Role of Cannabinoid Receptors in Crocin-Induced Hypoalgesia in Neuropathic Pain in Rats

Purpose: Neuropathic pain involves injury or alteration of the normal sensory and modulatory nervous systems to produce a set of symptoms that are often difficult to treat. Previous study indicates that crocin has anti-inflammatory properties that may be mediated by the neurotransmitter system. In this study, we determine if there is an interaction between crocin and the cannabinoid system on chronic constriction injury (CCI)-induced neuropathic pain in male rats.

Materials and methods: In this experimental study, adult male Wistar rats (220-250 g) were used. CCI was induced by setting four loose ligatures around the sciatic nerve. In part 1, after nerve lesion, vehicle, crocin (60 mg/kg) or Win 55-212-2 (0.1 mg/kg) as an agonist and AM 251 (0.1 mg/kg) as an antagonist of cannabinoid receptors were injected intraperitoneally daily in separate groups for 2 weeks. In part 2, two weeks after nerve lesion, vehicle (5 µL), crocin (6 µg/5 µL), Win 55-212-2 (0.1 µg/5 µL), AM 251 (0.1 µg/5 µL) were administered intracerebroventricularly (ICV) in separate groups. Mechanical allodynia and thermal hyperalgesia were measured using Von Frey filaments and plantar test device, respectively, at day 14. Data were analyzed by two-way ANOVA and Sidak's multiple comparisons post-test.

Results: Results indicated that centrally administered crocin significantly decreased thermal hyperalgesia and mechanical allodynia. Also, peripheral injection of crocin significantly decreased mechanical allodynia but not thermal hyperalgesia. Central or peripheral administration of Win 55-212-2 or AM 251 modulates the analgesic effect of crocin significantly.

Conclusion: Our findings showed that crocin has significant analgesic effects that are probably mediated by an endocannabinoid mechanism.

Keywords: AM 251; Win 55-212-2; neuropathic pain; rat; crocin.