Undergraduate Honors Theses

Thesis Defended

Spring 2013

Document Type

Thesis

Department

Psychology & Neuroscience

First Advisor

Dr. Lina Watkinds

Second Advisor

Dr. Peter Grace

Abstract

Opioids are a frontline clinical therapy for the treatment of neuropathic pain. Yet, opioid use is fraught with many negative side effects. This study investigates the effect of repeated morphine following peripheral nerve constriction on mechanical allodynia and central immune activation in rats. Mild chronic constriction injury (CCI) was performed on Sprague Dawley rats by tying one chromic gut suture around the sciatic nerve. Following surgery, morphine (5 mg/kg) was administered twice daily for 5 days. Mechanical allodynia was assessed using the von Frey method. The magnitude of CCI-allodynia was potentiated by morphine at 1 day post-dosing, and the effect remained at 35 days post-dosing (n=11-12, p<0.001). The duration of CCI-allodynia was also potentiated by subsequent morphine in Fischer 344 rats (n=6, p<0.001 at day 35 post-dosing). Immunohistochemistry was used in the dorsal horn of the lumbar spinal cord at 1 and 21 days post-dosing in Sprague Dawley rats. No interaction between CCI and morphine was found to increase expression of either CD11b or GFAP. In the Sprague Dawley rats, intrathecal blockade of TLR4 using (+)-naloxone during morphine administration inhibited subsequent potentiation of allodynia (n=6, p<0.05 at day 28 post-dosing). Additionally, acute intrathecal blockade of IL-1 receptors 44 days post-morphine transiently reversed established potentiation of allodynia (n=4, p<0.001 at 1, 2, 4, and 6 hours post-dosing). Together, these findings suggest that repeated morphine following nerve injury potentiates both the magnitude and duration of allodynia, at least in part via TLR4 and the enduring release of IL-1.

Share

COinS