-nociceptive effect of peripheral serotonin 5-HT2B receptor activation on neuropathic pain.. PAIN, Elsevier, 2012, 153 (6), pp.1320-31. <10.1016/j.pain.2012.03.024>. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 receptor. CCI resulted in a biphasic upregulation of 5-HT 2B receptor expression in lumbar dorsal root ganglia, consisting of a transient early increase (23-fold), two days after surgery, before the development of neuropathic pain, followed by a steady, five times increase, levels remaining constant thereafter until the pain disappeared. 5-HT 2B receptors were immmunolocalized mostly on primary sensory neurons and infiltrating macrophages. Intrathecal injection of RS127445, a selective 5-HT 2B receptor antagonist, enhanced mechanical and cold allodynia. A single application of BW732C86, a 5-HT 2B agonist, to the sciatic nerve immediately after ligature completely prevented mechanical allodynia and significantly decreased cold allodynia. This effect was dose-dependent and reversed by a 5-HT 2B antagonist. We also observed a marked decrease in macrophage infiltration of the sciatic nerve, neuropathic pain markers and cytokine induction. Our data reveal the relationships between serotonin, the immune system and neuropathic pain, and demonstrate a critical role of 5-HT 2Breceptors in blood-derived macrophages.

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