The effects of chronic neuropathic pain on the self-administration of highly potent MOR agonist, fentanyl

Abstract

There is significant overlap between chronic pain and opioid use disorder (OUD) patient populations such that approximately 50-65% of chronic pain patients have OUD. However, we understand relatively little about how chronic, long-lasting pain states alter ongoing self-administration of opioid analgesics. Thus, the goal of this study was to determine if chronic neuropathic pain altered the ongoing self-administration of fentanyl, or a non-opioid drug of abuse, cocaine. Animals were trained to self-administer fentanyl or cocaine in a multi-dose self-administration procedure composed of five 25-min components, exposing animals to multiple doses of drug per day. Operant behavior was established prior to induction of chronic pain via the spared nerve injury (SNI). Animals were allowed 72 hours of post-operative recovery and resumed self-administration on post-operative day 4. All animals dose-dependently self-administered fentanyl prior to surgery. On post-operative day 4, both sham and SNI groups showed a significant decrease in fentanyl self-administration. By post-operative day 9, fentanyl intake was no longer significantly different from pre-surgical intake. Over the course of 4 weeks of self-administration, there was an increase in intake of specifically the 10 ug/kg/inf dose of fentanyl. Cocaine self-administration was not altered at any point following either surgery. Collectively, these results suggest that SNI-induced hypersensitivity failed to alter the reinforcing effects of fentanyl, or non-opioid drug of abuse, cocaine. Future studies should evaluate the abuse potential of lower efficacy MOR agonists such as nalbuphine or buprenorphine, as small changes were observed in fentanyl-maintained behavior over time in both SNI and sham groups. Significance statementMOR agonists are excellent analgesics; however, they are not first-line treatments for chronic pain, in part due to abuse potential. This study demonstrates that small, significant rightward shifts in the fentanyl dose response curve were observed following induction of both sham and spared nerve injury (SNI) (chronic neuropathic pain-like) states, suggesting these changes were observed independent of pain state. These data indicate that SNI-induced neuropathic pain failed to alter the ongoing self-administration of highly potent MOR agonist, fentanyl.