Abstract
In the present study, we investigated the anti-inflammatory mechanisms by which gabapentin enhances morphine anti-nociceptive effect in neuropathic pain in rats and the interaction between the anti-nociceptive effects of gabapentin on morphine and the interleukin (IL)-10-heme-oxygenase (HO)-1 signal pathway in a rat model of neuropathic pain. The neuropathic pain model was induced via a left L5/6 spinal nerve ligation (SNL) in rats. The anti-nociceptive effect of gabapentin and IL-10 on morphine was examined over a 7-day period, and the effects of the anti-IL-10 and HO-1 inhibitor zinc protoporphyrin (ZnPP) on gabapentin/morphine co-injection were assessed. Drug administration was given over 7 days, and on day 8, both anti-inflammatory cytokine IL-10, a stress-induced protein HO-1 and pro-inflammatory cytokines IL-1β, IL-6 and TNF-α were measured. Gabapentin attenuated morphine tolerance over 7 days of co-administration, and reduced the expression of pro-inflammatory cytokines but increased IL-10 and HO-1 expression. The effect of gabapentin on morphine was partially blocked using the anti-IL-10 antibody or the HO-1 inhibitor zinc protoporphyrin. Our findings indicated that the anti-nociceptive effects of gabapentin on morphine might be caused by activation of the IL-10-HO-1 signalling pathway, which resulted in the inhibition of the expression of pro-inflammatory cytokines in neuropathic pain in the rat spinal cord.
Highlights
Neuropathic pain remains a serious clinical problem due to the lack of efficacy of available therapeutic modalities
We found that gabapentin-attenuated morphine tolerance is associated with the upregulation of spinal anti-inflammatory cytokine IL-10 and downregulation of proinflammatory cytokines TNF-α, IL-1β and IL-6
Effects of Gabapentin and Anti-IL-10 Antibody on Morphine Administration in spinal nerve ligation (SNL) Rats In SNL rats, chronic morphine tolerance was attenuated by coadministration of gabapentin with morphine twice a day for 7 days in the behavioural tests (Fig. 2b, c)
Summary
Neuropathic pain remains a serious clinical problem due to the lack of efficacy of available therapeutic modalities. Using opioids to control neuropathic pain has proven to be effective in animals and humans, challenges with analgesic tolerance have limited its use. The mechanism underlying opioid tolerance is complex and poorly understood under conditions of neuropathic pain. A deeper understanding of the mechanisms underlying morphine tolerance under conditions of neuropathic pain may contribute to the development of better analgesic treatments for pain. Opioids-induced hyperalgesia is observed in tolerance; it is similar to the symptoms observed in neuropathic pain, where opioids have a limited analgesic effect (Mika et al 2004; Narita et al 2013). Numerous studies have indicated that neuropathic pain results in reduced morphine efficacy and a more rapid development of morphine tolerance
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
