GAP JUNCTION (CONNEXIN-43) IS A DRUG TARGET FOR RELIEVING NEUROPATHIC PAIN IN RATS

Gap junctions are specialized intercellular channels that enable direct communication between adjacent cells like the glial cells in the central nervous system by ectopic firing of neurons. Glial facilitation, including activation of p38 MAPK in microglia after spinal nerve ligation has also been reported during pain transmission.The aim of the present study was to evaluate the role of connexin 43 gap junction channels in rodents after sciatic nerve damage. Sprague-Dawley male rats were subjected to partial sciatic nerve ligation (PSNL) surgery allodynia was recorded. Semi-quantitative estimation was done by Western blot. Microglial proliferation was noted by Immunofluorescence. Various blockers of Connexin-43 gap junction was administered systemically, again on day 14 and their anti-nociceptive effect evaluated using assessment of allodynia. Results: Allodynia a characteristic feature of neuropathic pain, was observed on day 14 after nerve ligation.Histological analysis showed nerve damage after ligation. Immunohistochemistry and Western blot experiments showed higher expression of Connexin-43 channel though not for Connexin 32 and 37 channels. There was increased number of microglia in the spinal cord. Blocking Connexin 43 gap junction channels showed anti-nociception at 3 hr after drug administration. Pannexin channel blocker also showed anti-nociception though not scrambled pannexin blocker. This anti-nociceptive effect was comparable to the standard dose of morphine in rats (10 mg/kg). Conclusion: The data show connexin-43 gap junction blockers to be effective in neuropathic pain state and this effect was similar or even better than morphine.