Fig. 2. P2Y12 antagonists, MRS2395 and clopidogrel, attenuated spinal nerve ligation (SNL)-induced pain behavior in rats.

a Schematic of the experimental timeline. Daily treatment with MRS2395 inhibited the mechanical allodynia (b) and thermal hyperalgesia (d) on the ipsilateral sides (b, d) and made no difference on the contralateral sides (c, e) after SNL surgery. MRS2395 was intrathecally injected three times a day, 200 μg per injection per rat, beginning from 1 day before surgery, and continuing for a further 5 days. MRS2395 reversed the mechanical allodynia for up to 7 days after surgery. Injury-induced thermal hyperalgesia was also suppressed by MRS2395 from day 1 to 5. There was no effect of MRS2395 on the mechanical allodynia and thermal hyperalgesia in the contralateral hind paw. Likewise, treatment with oral clopidogrel alleviated the mechanical allodynia (f) and thermal hyperalgesia (h) on the ipsilateral side (f, h), while the contralateral side was not affected (g, i). Oral clopidogrel was administered three times a day, 10 mg/kg per administration, beginning from 1 day before surgery and continuing for 6 days. Clopidogrel reversed the mechanical allodynia for up to 7 days after surgery. Injury-induced thermal hyperalgesia was also suppressed by clopidogrel from day 1 to 5. There was no effect of clopidogrel on the mechanical allodynia and thermal hyperalgesia in the contralateral hind paw. Values are represented as mean ± SEM, n = 6 rats per group. ^*p < 0.05, vs. sham group, ^**p < 0.01 vs. sham group, ^***p < 0.001 vs. sham group; ^#p < 0.05, vs. SNL group, ^##p < 0.01, vs. SNL group, ^###p < 0.001, vs. SNL group