Absence of C-C motif chemokine ligand 5 in mice leads to decreased local macrophage recruitment and behavioral hypersensitivity in a murine neuropathic pain model

作者：Liou Jiin Tarng; Yuan Hui Bih; Mao Chih Chieh; Lai Ying Shu; Day Yuan Ji^*

来源：Pain, 2012, 153(6): 1283-1291.

DOI：10.1016/j.pain.2012.03.008

• Neuropathic pain
• Chemokine
• CCL5
• Nerve injury
• Inflammation
• Animal model

Accumulated evidence suggests that the C-C motif chemokine ligand 5 (CCL5) modulates migration of inflammatory cells in several pathological conditions. This study tested the hypothesis that lack of CCL5 would modulate the recruitment of inflammatory cells to painful, inflamed sites and could attenuate pain in a murine chronic neuropathic pain model. Nociceptive sensitization, immune cell infiltration, multiple cytokine expression, and opioid peptide expression in damaged nerves were studied in wildtype (CCL5 +/+) and CCL5-deficient (CCL5 -/-) mice after partial sciatic nerve ligation (PSNL). Results indicated that CCL5 -/- mice had less behavioral hypersensitivity after PSNL. Macrophage infiltration and proinflammatory cytokines (tumor necrosis factor-alpha, interleukin [IL]-1 beta, IL-6, and interferon-c) in damaged nerves following PSNL were significantly decreased in CCL5 -/- mice. Conversely, several antiinflammatory cytokine (IL-4 and IL-10) proteins were significantly increased in CCL5 -/- animals and the expression of enkephalin, beta-endorphin, and dynorphin mRNA was significantly lower than in wild-type control mice. These results represent the first evidence that CCL5 is capable of regulating the pathway that controls hyperalgesia at the level of the peripheral injured site in a murine chronic neuropathic pain model. We demonstrated that lack of CCL5 modulated cell infiltration and the proinflammatory milieu within the injured nerve. Attenuated behavioral hypersensitivity in CCL5 -/- mice observed in the current study could be a result of decreased macrophage infiltration, mobilization, and functional ability at injured sites. Collectively, the present study results suggest that CCL5 receptor antagonists may ultimately provide a novel class of analgesics for therapeutic intervention in chronic neuropathic pain.

• 出版日期2012-6
• 单位长春大学