Study of the effect of GABAA receptore and glial inhibition on behavioral responses in CCI model of neuropathic pain in rat

• Main Authors: Mehi Sadeghi, Homa Manaheji, Abbad Haghparast, Jalal Zaringhalam, Samad Nazemi, Zahra Bahari
• Format: Article
• Language: English
• Published: Bushehr University of Medical Sciences 2015-01-01
• Series: Iranian South Medical Journal
• Subjects: neuropathic pain; hyperalgesia; allodynia; CCI; muscimol; pentoxifylline
• Online Access: http://ismj.bpums.ac.ir/browse.php?a_code=A-10-3-542&slc_lang=en&sid=1

Background: The mechanisms underlying neuropathic pain are complex and remain controversial. From the proposed mechanisms we can refer to loss of GABAergic inhibition and glial activation in the spinal dorsal horn. As for the discrepancies in the neuropathic pain mechanisms, in the present study, we examined whether the GABA-A receptor agonist muscimol and glial inhibitor pentoxifylline would modify behavioral tests in rats with Chronic Constriction Injury (CCI). Material and Methods: In this study male wistar rats (200-250 g) were used and for neuropathy induction, the CCI model (Bennett method, 1988) was used. In the sham group, after exposing the sciatic nerve, surgery region was closed. Pentoxifylline was administered one day before neuropathy to 14 days after CCI (30 mg/kg daily) and behavioral tests (plantar test and von frey) were performed one day before surgery and then on days 1, 4, 7 and 14 after surgery and 30 minutes after pentoxifylline adminstration .In groups that received muscimol with doses 0.5, 1 and 2 mg/kg on day 14 after CCI, behavioral tests were experienced before and 30 minutes after drug administration. Results: Behavioral assessment indicated that CCI induce symptoms of neuropathic pain but both muscimol and pentoxifylline could reduce pain behavioral responses. It seems that this reduction of muscimol (1 and 2 mg/kg) was more effective in thermal hyperalgesia than pentoxifylline, and for pentoxifylline (30 mg/kg) was more effective in mechanical allodynia than muscimol. Conclusion: present data showed that muscimol via activation of GABA-A receptors and pentoxifylline via glial inhibition reduced behavioral symptoms of neuropathic pain after spinal cord injury.