|
|
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char = i;code = 105
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char = g;code = 103
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char = i;code = 105
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char = l;code = 108
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char = m;code = 109
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char = t;code = 116
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char = r;code = 114
char = e;code = 101
char = c;code = 99
char = e;code = 101
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char = o;code = 111
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char = t;code = 116
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char = o;code = 111
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char = g;code = 103
char = h;code = 104
char = ;code = 32
char = h;code = 104
char = i;code = 105
char = s;code = 115
char = t;code = 116
char = o;code = 111
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char = e;code = 101
char = ;code = 32
char = H;code = 72
char = 3;code = 51
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char = a;code = 97
char = c;code = 99
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char = y;code = 121
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char = t;code = 116
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char = n;code = 110
char = ;code = 32
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char = n;code = 110
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char = e;code = 101
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char = p;code = 112
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char = e;code = 101
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char = l;code = 108
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char = e;code = 101
char = s;code = 115
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char = e;code = 101
char = l;code = 108
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char = c;code = 99
char = i;code = 105
char = t;code = 116
char = s;code = 115
char = ;code = 32
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char = r;code = 114
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char = p;code = 112
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char = t;code = 116
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char = c;code = 99
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char = p;code = 112
char = a;code = 97
char = i;code = 105
char = n;code = 110
char = .;code = 46
result sql = Epigenetic augmentation of the macrophage inflammatory protein 2/C-X-C chemokine receptor type 2 axis through histone H3 acetylation in injured peripheral nerves elicits neuropathic pain.
Epigenetic augmentation of the macrophage inflammatory protein 2/C-X-C chemokine receptor type 2 axis through histone H3 acetylation in injured peripheral nerves elicits neuropathic pain.char = A;code = 65
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char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = r;code = 114
char = e;code = 101
char = ;code = 32
char = i;code = 105
char = s;code = 115
char = ;code = 32
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char = o;code = 111
char = w;code = 119
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char = s;code = 115
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char = p;code = 112
char = h;code = 104
char = e;code = 101
char = n;code = 110
char = y;code = 121
char = l;code = 108
char = );code = 41
char = u;code = 117
char = r;code = 114
char = e;code = 101
char = a;code = 97
char = ;code = 32
char = (;code = 40
char = S;code = 83
char = B;code = 66
char = 2;code = 50
char = 2;code = 50
char = 5;code = 53
char = 0;code = 48
char = 0;code = 48
char = 2;code = 50
char = );code = 41
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = e;code = 101
char = v;code = 118
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = P;code = 80
char = S;code = 83
char = L;code = 76
char = -;code = 45
char = i;code = 105
char = n;code = 110
char = d;code = 100
char = u;code = 117
char = c;code = 99
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = t;code = 116
char = a;code = 97
char = c;code = 99
char = t;code = 116
char = i;code = 105
char = l;code = 108
char = e;code = 101
char = ;code = 32
char = a;code = 97
char = l;code = 108
char = l;code = 108
char = o;code = 111
char = d;code = 100
char = y;code = 121
char = n;code = 110
char = i;code = 105
char = a;code = 97
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = r;code = 114
char = m;code = 109
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = h;code = 104
char = y;code = 121
char = p;code = 112
char = e;code = 101
char = r;code = 114
char = a;code = 97
char = l;code = 108
char = g;code = 103
char = e;code = 101
char = s;code = 115
char = i;code = 105
char = a;code = 97
char = .;code = 46
char = ;code = 32
char = P;code = 80
char = e;code = 101
char = r;code = 114
char = i;code = 105
char = n;code = 110
char = e;code = 101
char = u;code = 117
char = r;code = 114
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = j;code = 106
char = e;code = 101
char = c;code = 99
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = c;code = 99
char = o;code = 111
char = m;code = 109
char = b;code = 98
char = i;code = 105
char = n;code = 110
char = a;code = 97
char = n;code = 110
char = t;code = 116
char = ;code = 32
char = M;code = 77
char = I;code = 73
char = P;code = 80
char = -;code = 45
char = 2;code = 50
char = ;code = 32
char = e;code = 101
char = l;code = 108
char = i;code = 105
char = c;code = 99
char = i;code = 105
char = t;code = 116
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = n;code = 110
char = e;code = 101
char = u;code = 117
char = r;code = 114
char = o;code = 111
char = p;code = 112
char = a;code = 97
char = t;code = 116
char = h;code = 104
char = i;code = 105
char = c;code = 99
char = ;code = 32
char = p;code = 112
char = a;code = 97
char = i;code = 105
char = n;code = 110
char = -;code = 45
char = l;code = 108
char = i;code = 105
char = k;code = 107
char = e;code = 101
char = ;code = 32
char = b;code = 98
char = e;code = 101
char = h;code = 104
char = a;code = 97
char = v;code = 118
char = i;code = 105
char = o;code = 111
char = r;code = 114
char = s;code = 115
char = .;code = 46
char = ;code = 32
char = A;code = 65
char = n;code = 110
char = t;code = 116
char = i;code = 105
char = -;code = 45
char = M;code = 77
char = I;code = 73
char = P;code = 80
char = -;code = 45
char = 2;code = 50
char = ;code = 32
char = s;code = 115
char = u;code = 117
char = p;code = 112
char = p;code = 112
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = s;code = 115
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = n;code = 110
char = e;code = 101
char = u;code = 117
char = t;code = 116
char = r;code = 114
char = o;code = 111
char = p;code = 112
char = h;code = 104
char = i;code = 105
char = l;code = 108
char = ;code = 32
char = a;code = 97
char = c;code = 99
char = c;code = 99
char = u;code = 117
char = m;code = 109
char = u;code = 117
char = l;code = 108
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = S;code = 83
char = C;code = 67
char = N;code = 78
char = ;code = 32
char = a;code = 97
char = f;code = 102
char = t;code = 116
char = e;code = 101
char = r;code = 114
char = ;code = 32
char = P;code = 80
char = S;code = 83
char = L;code = 76
char = .;code = 46
char = ;code = 32
char = N;code = 78
char = e;code = 101
char = u;code = 117
char = t;code = 116
char = r;code = 114
char = o;code = 111
char = p;code = 112
char = h;code = 104
char = i;code = 105
char = l;code = 108
char = ;code = 32
char = d;code = 100
char = e;code = 101
char = p;code = 112
char = l;code = 108
char = e;code = 101
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = b;code = 98
char = y;code = 121
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = t;code = 116
char = r;code = 114
char = a;code = 97
char = p;code = 112
char = e;code = 101
char = r;code = 114
char = i;code = 105
char = t;code = 116
char = o;code = 111
char = n;code = 110
char = e;code = 101
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = j;code = 106
char = e;code = 101
char = c;code = 99
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = L;code = 76
char = y;code = 121
char = 6;code = 54
char = G;code = 71
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = t;code = 116
char = i;code = 105
char = b;code = 98
char = o;code = 111
char = d;code = 100
char = y;code = 121
char = ;code = 32
char = a;code = 97
char = t;code = 116
char = t;code = 116
char = e;code = 101
char = n;code = 110
char = u;code = 117
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = P;code = 80
char = S;code = 83
char = L;code = 76
char = -;code = 45
char = i;code = 105
char = n;code = 110
char = d;code = 100
char = u;code = 117
char = c;code = 99
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = n;code = 110
char = e;code = 101
char = u;code = 117
char = r;code = 114
char = o;code = 111
char = p;code = 112
char = a;code = 97
char = t;code = 116
char = h;code = 104
char = i;code = 105
char = c;code = 99
char = ;code = 32
char = p;code = 112
char = a;code = 97
char = i;code = 105
char = n;code = 110
char = .;code = 46
char = ;code = 32
char = B;code = 66
char = o;code = 111
char = t;code = 116
char = h;code = 104
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = t;code = 116
char = i;code = 105
char = -;code = 45
char = M;code = 77
char = I;code = 73
char = P;code = 80
char = -;code = 45
char = 2;code = 50
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = S;code = 83
char = B;code = 66
char = 2;code = 50
char = 2;code = 50
char = 5;code = 53
char = 0;code = 48
char = 0;code = 48
char = 2;code = 50
char = ;code = 32
char = s;code = 115
char = u;code = 117
char = p;code = 112
char = p;code = 112
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = s;code = 115
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = u;code = 117
char = p;code = 112
char = -;code = 45
char = r;code = 114
char = e;code = 101
char = g;code = 103
char = u;code = 117
char = l;code = 108
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = f;code = 102
char = l;code = 108
char = a;code = 97
char = m;code = 109
char = m;code = 109
char = a;code = 97
char = t;code = 116
char = o;code = 111
char = r;code = 114
char = y;code = 121
char = ;code = 32
char = c;code = 99
char = y;code = 121
char = t;code = 116
char = o;code = 111
char = k;code = 107
char = i;code = 105
char = n;code = 110
char = e;code = 101
char = s;code = 115
char = ;code = 32
char = a;code = 97
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char = d;code = 100
char = ;code = 32
char = c;code = 99
char = h;code = 104
char = e;code = 101
char = m;code = 109
char = o;code = 111
char = k;code = 107
char = i;code = 105
char = n;code = 110
char = e;code = 101
char = s;code = 115
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = j;code = 106
char = u;code = 117
char = r;code = 114
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = S;code = 83
char = C;code = 67
char = N;code = 78
char = .;code = 46
char = ;code = 32
char = I;code = 73
char = n;code = 110
char = ;code = 32
char = a;code = 97
char = d;code = 100
char = d;code = 100
char = i;code = 105
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ,;code = 44
char = ;code = 32
char = a;code = 97
char = c;code = 99
char = e;code = 101
char = t;code = 116
char = y;code = 121
char = l;code = 108
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = h;code = 104
char = i;code = 105
char = s;code = 115
char = t;code = 116
char = o;code = 111
char = n;code = 110
char = e;code = 101
char = ;code = 32
char = H;code = 72
char = 3;code = 51
char = ;code = 32
char = [;code = 91
char = l;code = 108
char = y;code = 121
char = s;code = 115
char = i;code = 105
char = n;code = 110
char = e;code = 101
char = ;code = 32
char = (;code = 40
char = L;code = 76
char = y;code = 121
char = s;code = 115
char = 9;code = 57
char = );code = 41
char = -;code = 45
char = a;code = 97
char = c;code = 99
char = e;code = 101
char = t;code = 116
char = y;code = 121
char = l;code = 108
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = h;code = 104
char = i;code = 105
char = s;code = 115
char = t;code = 116
char = o;code = 111
char = n;code = 110
char = e;code = 101
char = ;code = 32
char = H;code = 72
char = 3;code = 51
char = ;code = 32
char = (;code = 40
char = A;code = 65
char = c;code = 99
char = K;code = 75
char = 9;code = 57
char = -;code = 45
char = H;code = 72
char = 3;code = 51
char = );code = 41
char = ];code = 93
char = ;code = 32
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = o;code = 111
char = m;code = 109
char = o;code = 111
char = t;code = 116
char = e;code = 101
char = r;code = 114
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = g;code = 103
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = M;code = 77
char = I;code = 73
char = P;code = 80
char = -;code = 45
char = 2;code = 50
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = C;code = 67
char = X;code = 88
char = C;code = 67
char = R;code = 82
char = 2;code = 50
char = ;code = 32
char = w;code = 119
char = a;code = 97
char = s;code = 115
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = c;code = 99
char = r;code = 114
char = e;code = 101
char = a;code = 97
char = s;code = 115
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = j;code = 106
char = u;code = 117
char = r;code = 114
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = S;code = 83
char = C;code = 67
char = N;code = 78
char = ;code = 32
char = a;code = 97
char = f;code = 102
char = t;code = 116
char = e;code = 101
char = r;code = 114
char = ;code = 32
char = P;code = 80
char = S;code = 83
char = L;code = 76
char = .;code = 46
char = ;code = 32
char = E;code = 69
char = x;code = 120
char = p;code = 112
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = s;code = 115
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = A;code = 65
char = c;code = 99
char = K;code = 75
char = 9;code = 57
char = -;code = 45
char = H;code = 72
char = 3;code = 51
char = ;code = 32
char = w;code = 119
char = a;code = 97
char = s;code = 115
char = ;code = 32
char = o;code = 111
char = b;code = 98
char = s;code = 115
char = e;code = 101
char = r;code = 114
char = v;code = 118
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = i;code = 105
char = n;code = 110
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char = t;code = 116
char = h;code = 104
char = e;code = 101
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char = n;code = 110
char = u;code = 117
char = c;code = 99
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char = e;code = 101
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char = o;code = 111
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char = ;code = 32
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char = e;code = 101
char = u;code = 117
char = t;code = 116
char = r;code = 114
char = o;code = 111
char = p;code = 112
char = h;code = 104
char = i;code = 105
char = l;code = 108
char = s;code = 115
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char = a;code = 97
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char = d;code = 100
char = ;code = 32
char = m;code = 109
char = a;code = 97
char = c;code = 99
char = r;code = 114
char = o;code = 111
char = p;code = 112
char = h;code = 104
char = a;code = 97
char = g;code = 103
char = e;code = 101
char = s;code = 115
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char = s;code = 115
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char = r;code = 114
char = r;code = 114
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char = n;code = 110
char = d;code = 100
char = i;code = 105
char = n;code = 110
char = g;code = 103
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char = t;code = 116
char = h;code = 104
char = e;code = 101
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char = e;code = 101
char = p;code = 112
char = i;code = 105
char = n;code = 110
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char = u;code = 117
char = r;code = 114
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char = u;code = 117
char = m;code = 109
char = .;code = 46
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char = A;code = 65
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char = i;code = 105
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char = s;code = 115
char = t;code = 116
char = r;code = 114
char = a;code = 97
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char = i;code = 105
char = o;code = 111
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char = ;code = 32
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char = e;code = 101
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char = h;code = 104
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char = s;code = 115
char = t;code = 116
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char = e;code = 101
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char = a;code = 97
char = c;code = 99
char = e;code = 101
char = t;code = 116
char = y;code = 121
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char = a;code = 97
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char = e;code = 101
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char = a;code = 97
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char = e;code = 101
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char = i;code = 105
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char = h;code = 104
char = i;code = 105
char = b;code = 98
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char = t;code = 116
char = o;code = 111
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char = a;code = 97
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char = a;code = 97
char = c;code = 99
char = a;code = 97
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char = i;code = 105
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char = a;code = 97
char = c;code = 99
char = i;code = 105
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char = s;code = 115
char = u;code = 117
char = p;code = 112
char = p;code = 112
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = s;code = 115
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
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char = u;code = 117
char = p;code = 112
char = -;code = 45
char = r;code = 114
char = e;code = 101
char = g;code = 103
char = u;code = 117
char = l;code = 108
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = M;code = 77
char = I;code = 73
char = P;code = 80
char = -;code = 45
char = 2;code = 50
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = C;code = 67
char = X;code = 88
char = C;code = 67
char = R;code = 82
char = 2;code = 50
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = S;code = 83
char = C;code = 67
char = N;code = 78
char = ;code = 32
char = a;code = 97
char = f;code = 102
char = t;code = 116
char = e;code = 101
char = r;code = 114
char = ;code = 32
char = P;code = 80
char = S;code = 83
char = L;code = 76
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = u;code = 117
char = l;code = 108
char = t;code = 116
char = e;code = 101
char = d;code = 100
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char = i;code = 105
char = n;code = 110
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char = t;code = 116
char = h;code = 104
char = e;code = 101
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char = p;code = 112
char = r;code = 114
char = e;code = 101
char = v;code = 118
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = o;code = 111
char = f;code = 102
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result sql = Although there is growing evidence showing that the involvement of chemokines in the pathogenesis of neuropathic pain is associated with neuroinflammation, the details are unclear. We investigated the C-X-C chemokine ligand type 2 [macrophage inflammatory protein 2 (MIP-2)]/C-X-C chemokine receptor type 2 (CXCR2) axis and epigenetic regulation of these molecules in neuropathic pain after peripheral nerve injury. Expression of MIP-2 and CXCR2 were up-regulated and localized on accumulated neutrophils and macrophages in the injured sciatic nerve (SCN) after partial sciatic nerve ligation (PSL). Perineural injection of MIP-2-neutralizing antibody (anti-MIP-2) or the CXCR2 antagonist N-(2-bromophenyl)-N'-(2-hydroxy-4-nitrophenyl)urea (SB225002) prevented PSL-induced tactile allodynia and thermal hyperalgesia. Perineural injection of recombinant MIP-2 elicited neuropathic pain-like behaviors. Anti-MIP-2 suppressed neutrophil accumulation in the SCN after PSL. Neutrophil depletion by intraperitoneal injection of Ly6G antibody attenuated PSL-induced neuropathic pain. Both anti-MIP-2 and SB225002 suppressed up-regulation of inflammatory cytokines and chemokines in the injured SCN. In addition, acetylation of histone H3 [lysine (Lys9)-acetylated histone H3 (AcK9-H3)] on the promoter region of MIP-2 and CXCR2 was increased in the injured SCN after PSL. Expression of AcK9-H3 was observed in the nuclei of neutrophils and macrophages surrounding the epineurium. Administration of the histone acetyltransferase inhibitor anacardic acid suppressed the up-regulation of MIP-2 and CXCR2 in the SCN after PSL and resulted in the prevention of PSL-induced neuropathic pain. Taken together, these results show that augmentation of the MIP-2/CXCR2 axis by hyperacetylation of histone H3 on the promoter region of MIP-2 and CXCR2 located in the injured peripheral nerve elicits chronic neuroinflammation through neutrophil accumulation, leading to neuropathic pain.
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result sql = Epigenetic augmentation of the macrophage inflammatory protein 2/C-X-C chemokine receptor type 2 axis through histone H3 acetylation in injured peripheral nerves elicits neuropathic pain.
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char = a;code = 97
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char = t;code = 116
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char = r;code = 114
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char = e;code = 101
char = r;code = 114
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char = p;code = 112
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char = a;code = 97
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char = r;code = 114
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char = e;code = 101
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char = j;code = 106
char = u;code = 117
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char = ;code = 32
char = E;code = 69
char = x;code = 120
char = p;code = 112
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = s;code = 115
char = i;code = 105
char = o;code = 111
char = n;code = 110
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char = o;code = 111
char = f;code = 102
char = ;code = 32
char = M;code = 77
char = I;code = 73
char = P;code = 80
char = -;code = 45
char = 2;code = 50
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = C;code = 67
char = X;code = 88
char = C;code = 67
char = R;code = 82
char = 2;code = 50
char = ;code = 32
char = w;code = 119
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char = r;code = 114
char = e;code = 101
char = ;code = 32
char = u;code = 117
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char = -;code = 45
char = r;code = 114
char = e;code = 101
char = g;code = 103
char = u;code = 117
char = l;code = 108
char = a;code = 97
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char = e;code = 101
char = d;code = 100
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char = a;code = 97
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char = d;code = 100
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char = l;code = 108
char = o;code = 111
char = c;code = 99
char = a;code = 97
char = l;code = 108
char = i;code = 105
char = z;code = 122
char = e;code = 101
char = d;code = 100
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char = o;code = 111
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char = ;code = 32
char = a;code = 97
char = c;code = 99
char = c;code = 99
char = u;code = 117
char = m;code = 109
char = u;code = 117
char = l;code = 108
char = a;code = 97
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char = e;code = 101
char = d;code = 100
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char = n;code = 110
char = e;code = 101
char = u;code = 117
char = t;code = 116
char = r;code = 114
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char = p;code = 112
char = h;code = 104
char = i;code = 105
char = l;code = 108
char = s;code = 115
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char = a;code = 97
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char = d;code = 100
char = ;code = 32
char = m;code = 109
char = a;code = 97
char = c;code = 99
char = r;code = 114
char = o;code = 111
char = p;code = 112
char = h;code = 104
char = a;code = 97
char = g;code = 103
char = e;code = 101
char = s;code = 115
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = j;code = 106
char = u;code = 117
char = r;code = 114
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = s;code = 115
char = c;code = 99
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char = a;code = 97
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char = i;code = 105
char = c;code = 99
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char = n;code = 110
char = e;code = 101
char = r;code = 114
char = v;code = 118
char = e;code = 101
char = ;code = 32
char = (;code = 40
char = S;code = 83
char = C;code = 67
char = N;code = 78
char = );code = 41
char = ;code = 32
char = a;code = 97
char = f;code = 102
char = t;code = 116
char = e;code = 101
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char = ;code = 32
char = p;code = 112
char = a;code = 97
char = r;code = 114
char = t;code = 116
char = i;code = 105
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = s;code = 115
char = c;code = 99
char = i;code = 105
char = a;code = 97
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char = i;code = 105
char = c;code = 99
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char = n;code = 110
char = e;code = 101
char = r;code = 114
char = v;code = 118
char = e;code = 101
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char = l;code = 108
char = i;code = 105
char = g;code = 103
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
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char = ;code = 32
char = (;code = 40
char = P;code = 80
char = S;code = 83
char = L;code = 76
char = );code = 41
char = .;code = 46
char = ;code = 32
char = P;code = 80
char = e;code = 101
char = r;code = 114
char = i;code = 105
char = n;code = 110
char = e;code = 101
char = u;code = 117
char = r;code = 114
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = j;code = 106
char = e;code = 101
char = c;code = 99
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = M;code = 77
char = I;code = 73
char = P;code = 80
char = -;code = 45
char = 2;code = 50
char = -;code = 45
char = n;code = 110
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char = u;code = 117
char = t;code = 116
char = r;code = 114
char = a;code = 97
char = l;code = 108
char = i;code = 105
char = z;code = 122
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = t;code = 116
char = i;code = 105
char = b;code = 98
char = o;code = 111
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char = y;code = 121
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char = a;code = 97
char = n;code = 110
char = t;code = 116
char = i;code = 105
char = -;code = 45
char = M;code = 77
char = I;code = 73
char = P;code = 80
char = -;code = 45
char = 2;code = 50
char = );code = 41
char = ;code = 32
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = C;code = 67
char = X;code = 88
char = C;code = 67
char = R;code = 82
char = 2;code = 50
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char = a;code = 97
char = n;code = 110
char = t;code = 116
char = a;code = 97
char = g;code = 103
char = o;code = 111
char = n;code = 110
char = i;code = 105
char = s;code = 115
char = t;code = 116
char = ;code = 32
char = N;code = 78
char = -;code = 45
char = (;code = 40
char = 2;code = 50
char = -;code = 45
char = b;code = 98
char = r;code = 114
char = o;code = 111
char = m;code = 109
char = o;code = 111
char = p;code = 112
char = h;code = 104
char = e;code = 101
char = n;code = 110
char = y;code = 121
char = l;code = 108
char = );code = 41
char = -;code = 45
char = N;code = 78
char = ';code = 39
char = -;code = 45
char = (;code = 40
char = 2;code = 50
char = -;code = 45
char = h;code = 104
char = y;code = 121
char = d;code = 100
char = r;code = 114
char = o;code = 111
char = x;code = 120
char = y;code = 121
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char = 4;code = 52
char = -;code = 45
char = n;code = 110
char = i;code = 105
char = t;code = 116
char = r;code = 114
char = o;code = 111
char = p;code = 112
char = h;code = 104
char = e;code = 101
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char = y;code = 121
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char = );code = 41
char = u;code = 117
char = r;code = 114
char = e;code = 101
char = a;code = 97
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char = (;code = 40
char = S;code = 83
char = B;code = 66
char = 2;code = 50
char = 2;code = 50
char = 5;code = 53
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char = 0;code = 48
char = 2;code = 50
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char = v;code = 118
char = e;code = 101
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char = e;code = 101
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char = ;code = 32
char = P;code = 80
char = S;code = 83
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char = -;code = 45
char = i;code = 105
char = n;code = 110
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char = u;code = 117
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char = d;code = 100
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char = t;code = 116
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char = e;code = 101
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char = a;code = 97
char = l;code = 108
char = l;code = 108
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char = d;code = 100
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char = i;code = 105
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char = a;code = 97
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char = d;code = 100
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char = t;code = 116
char = h;code = 104
char = e;code = 101
char = r;code = 114
char = m;code = 109
char = a;code = 97
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char = h;code = 104
char = y;code = 121
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char = a;code = 97
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char = g;code = 103
char = e;code = 101
char = s;code = 115
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char = a;code = 97
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char = P;code = 80
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char = n;code = 110
char = e;code = 101
char = u;code = 117
char = r;code = 114
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char = j;code = 106
char = e;code = 101
char = c;code = 99
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char = o;code = 111
char = n;code = 110
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char = o;code = 111
char = f;code = 102
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char = c;code = 99
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char = b;code = 98
char = i;code = 105
char = n;code = 110
char = a;code = 97
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char = t;code = 116
char = ;code = 32
char = M;code = 77
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char = P;code = 80
char = -;code = 45
char = 2;code = 50
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char = e;code = 101
char = l;code = 108
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char = c;code = 99
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char = p;code = 112
char = a;code = 97
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char = h;code = 104
char = i;code = 105
char = c;code = 99
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char = a;code = 97
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char = l;code = 108
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char = k;code = 107
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char = b;code = 98
char = e;code = 101
char = h;code = 104
char = a;code = 97
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char = i;code = 105
char = o;code = 111
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char = s;code = 115
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char = A;code = 65
char = n;code = 110
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char = i;code = 105
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char = M;code = 77
char = I;code = 73
char = P;code = 80
char = -;code = 45
char = 2;code = 50
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char = s;code = 115
char = u;code = 117
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char = e;code = 101
char = d;code = 100
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char = u;code = 117
char = t;code = 116
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char = h;code = 104
char = i;code = 105
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char = a;code = 97
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char = l;code = 108
char = a;code = 97
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char = i;code = 105
char = o;code = 111
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char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = S;code = 83
char = C;code = 67
char = N;code = 78
char = ;code = 32
char = a;code = 97
char = f;code = 102
char = t;code = 116
char = e;code = 101
char = r;code = 114
char = ;code = 32
char = P;code = 80
char = S;code = 83
char = L;code = 76
char = .;code = 46
char = ;code = 32
char = N;code = 78
char = e;code = 101
char = u;code = 117
char = t;code = 116
char = r;code = 114
char = o;code = 111
char = p;code = 112
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char = b;code = 98
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char = a;code = 97
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char = e;code = 101
char = a;code = 97
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char = c;code = 99
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char = o;code = 111
char = f;code = 102
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char = L;code = 76
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char = a;code = 97
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char = i;code = 105
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char = B;code = 66
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char = a;code = 97
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char = M;code = 77
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char = -;code = 45
char = 2;code = 50
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char = a;code = 97
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char = d;code = 100
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char = S;code = 83
char = B;code = 66
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char = 5;code = 53
char = 0;code = 48
char = 0;code = 48
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char = s;code = 115
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char = e;code = 101
char = d;code = 100
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char = l;code = 108
char = a;code = 97
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char = l;code = 108
char = a;code = 97
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char = o;code = 111
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char = y;code = 121
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char = c;code = 99
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char = u;code = 117
char = r;code = 114
char = e;code = 101
char = d;code = 100
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char = S;code = 83
char = C;code = 67
char = N;code = 78
char = .;code = 46
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char = I;code = 73
char = n;code = 110
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char = a;code = 97
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char = i;code = 105
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char = s;code = 115
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char = e;code = 101
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char = H;code = 72
char = 3;code = 51
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char = l;code = 108
char = y;code = 121
char = s;code = 115
char = i;code = 105
char = n;code = 110
char = e;code = 101
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char = (;code = 40
char = L;code = 76
char = y;code = 121
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char = );code = 41
char = -;code = 45
char = a;code = 97
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char = a;code = 97
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char = e;code = 101
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char = s;code = 115
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char = o;code = 111
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char = e;code = 101
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char = H;code = 72
char = 3;code = 51
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char = (;code = 40
char = A;code = 65
char = c;code = 99
char = K;code = 75
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char = -;code = 45
char = H;code = 72
char = 3;code = 51
char = );code = 41
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result sql = Although there is growing evidence showing that the involvement of chemokines in the pathogenesis of neuropathic pain is associated with neuroinflammation, the details are unclear. We investigated the C-X-C chemokine ligand type 2 [macrophage inflammatory protein 2 (MIP-2)]/C-X-C chemokine receptor type 2 (CXCR2) axis and epigenetic regulation of these molecules in neuropathic pain after peripheral nerve injury. Expression of MIP-2 and CXCR2 were up-regulated and localized on accumulated neutrophils and macrophages in the injured sciatic nerve (SCN) after partial sciatic nerve ligation (PSL). Perineural injection of MIP-2-neutralizing antibody (anti-MIP-2) or the CXCR2 antagonist N-(2-bromophenyl)-N'-(2-hydroxy-4-nitrophenyl)urea (SB225002) prevented PSL-induced tactile allodynia and thermal hyperalgesia. Perineural injection of recombinant MIP-2 elicited neuropathic pain-like behaviors. Anti-MIP-2 suppressed neutrophil accumulation in the SCN after PSL. Neutrophil depletion by intraperitoneal injection of Ly6G antibody attenuated PSL-induced neuropathic pain. Both anti-MIP-2 and SB225002 suppressed up-regulation of inflammatory cytokines and chemokines in the injured SCN. In addition, acetylation of histone H3 [lysine (Lys9)-acetylated histone H3 (AcK9-H3)] on the promoter region of MIP-2 and CXCR2 was increased in the injured SCN after PSL. Expression of AcK9-H3 was observed in the nuclei of neutrophils and macrophages surrounding the epineurium. Administration of the histone acetyltransferase inhibitor anacardic acid suppressed the up-regulation of MIP-2 and CXCR2 in the SCN after PSL and resulted in the prevention of PSL-induced neuropathic pain. Taken together, these results show that augmentation of the MIP-2/CXCR2 axis by hyperacetylation of histone H3 on the promoter region of MIP-2 and CXCR2 located in the injured peripheral nerve elicits chronic neuroinflammation through neutrophil accumulation, leading to neuropathic pain.
Publication: J. Pharmacol. Exp. Ther. 2012 Mar ;340(3)::577-87. :doi: 10.1124/jpet.111.187724.
Publication Date: 2012 Mar
Study Author(s): Kiguchi, Norikazu;Kobayashi, Yuka;Maeda, Takehiko;Fukazawa, Yohji;Tohya, Kazuo;Kimura, Michio;Kishioka, Shiroh;
Institution: Department of Pharmacology, Wakayama Medical University, 811-1 Kimiidera, Wakayama, Wakayama 641-0012, Japan.
Shortcut link to this study:
Publication Date: 2012 Mar
Study Author(s): Kiguchi, Norikazu;Kobayashi, Yuka;Maeda, Takehiko;Fukazawa, Yohji;Tohya, Kazuo;Kimura, Michio;Kishioka, Shiroh;
Institution: Department of Pharmacology, Wakayama Medical University, 811-1 Kimiidera, Wakayama, Wakayama 641-0012, Japan.
Shortcut link to this study:
Although there is growing evidence showing that the involvement of chemokines in the pathogenesis of neuropathic pain is associated with neuroinflammation, the details are unclear. We investigated the C-X-C chemokine ligand type 2 [macrophage inflammatory protein 2 (MIP-2)]/C-X-C chemokine receptor type 2 (CXCR2) axis and epigenetic regulation of these molecules in neuropathic pain after peripheral nerve injury. Expression of MIP-2 and CXCR2 were up-regulated and localized on accumulated neutrophils and macrophages in the injured sciatic nerve (SCN) after partial sciatic nerve ligation (PSL). Perineural injection of MIP-2-neutralizing antibody (anti-MIP-2) or the CXCR2 antagonist N-(2-bromophenyl)-N'-(2-hydroxy-4-nitrophenyl)urea (SB225002) prevented PSL-induced tactile allodynia and thermal hyperalgesia. Perineural injection of recombinant MIP-2 elicited neuropathic pain-like behaviors. Anti-MIP-2 suppressed neutrophil accumulation in the SCN after PSL. Neutrophil depletion by intraperitoneal injection of Ly6G antibody attenuated PSL-induced neuropathic pain. Both anti-MIP-2 and SB225002 suppressed up-regulation of inflammatory cytokines and chemokines in the injured SCN. In addition, acetylation of histone H3 [lysine (Lys9)-acetylated histone H3 (AcK9-H3)] on the promoter region of MIP-2 and CXCR2 was increased in the injured SCN after PSL. Expression of AcK9-H3 was observed in the nuclei of neutrophils and macrophages surrounding the epineurium. Administration of the histone acetyltransferase inhibitor anacardic acid suppressed the up-regulation of MIP-2 and CXCR2 in the SCN after PSL and resulted in the prevention of PSL-induced neuropathic pain. Taken together, these results show that augmentation of the MIP-2/CXCR2 axis by hyperacetylation of histone H3 on the promoter region of MIP-2 and CXCR2 located in the injured peripheral nerve elicits chronic neuroinflammation through neutrophil accumulation, leading to neuropathic pain.
PMID: 22135382
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