Involvement of CCL1/CCR8 in Spinal Cord Dorsal Horn in Remifentanil-Induced Hyperalgesia in Rats

Abstract

Background: Numerous researches manifested that remifentanil infusion might be responsible for opioid-induced hyperalgesia (OIH), but most studies exploring OIH were hardly designed to clarify underlying mechanisms. Chemokine (C-C motif) ligand 1 (CCL1) was found to be implicated in neuropathic pain, and our previous study has also shown that proinflammatory cytokines have been associated with the induction and maintenance of OIH. However, whether CCL1 could contribute to hyperalgesia induced by remifentanil in rats remains unclear.Methods: To explore effect of CCL1 on OIH, a neutralizing antibody against CCL1 (anti-CCL1) was administrated intrathecally after remifentanil infusion in rats. Western blotting and immunohistochemistry (IHC) were applied to analyze time course of CCL1 and CCR8 (specific CCL1 receptor) expression in dorsal horn after remifentanil administration. Expression of inflammatory mediators such as tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, and IL-6 was evaluated by real-time quantitative polymerase chain reaction (RT-qPCR). Paw withdrawal threshold (PWT) and paw withdrawal latency (PWL) were measured and recorded for 48 post-infusion hours to evaluate mechanical and thermal hyperalgesia.Results: We discovered that CCL1 and CCR8 expressions in dorsal horn were increased and maintained at a high level from 2 hours to 48 hours, the last examination time, after remifentanil infusion. We found that intrathecal delivery of anti-CCL1 could ameliorate remifentanil related thermal and mechanical hyperalgesia without affecting baseline nociceptive threshold. It was also shown that enhancement of inflammatory mediators (TNF-α, IL-1β, and IL-6) expression in dorsal horn after remifentanil infusion was reversed by anti-CCL1 administration.Conclusions: Our current results indicated that CCL1 and CCR8 might be implicated in the development of remifentanil-induced hyperalgesia via regulation of cytokines (TNF-α, IL-1β, and IL-6) in dorsal horn in rats. Citation: Lin- Lin Zhang, Rui- Chen Shu, Nan Li, Zhi-Fen Wang, Chun-Yan Wang, Hai- Yun Wang, et al. Involvement of CCL1/CCR8 in spinal cord dorsal horn in remifentanil- induced hyperalgesia in rats. J Anesth Perioper Med 2015; 2: 53-60. doi: 10.24015/JAPM.2015.0009This is an open-access article, published by Evidence Based Communications (EBC). This work is licensed under the Creative Commons Attribution 4.0 International License, which permits unrestricted use, distribution, and reproduction in any medium or format for any lawful purpose. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.