Role of spinal GABAA receptor reduction induced by stress in rat thermal hyperalgesia

Abstract

The mechanisms underlying stress-induced hyperalgesia (SIH) remain poorly understood. Recent findings have provided strong evidence indicating that SIH could be related, at least in part, to alterations in spinal cord GABA activity. In the present study, we first investigated how acute restraint stress impacted pain responses as assessed using the tail flick immersion test. These results showed that rats developed hyperalgesia at 6 h after being subjected to 1-h acute restraint stress. Second, we measured the activation of spinal neurons and alterations in expression of GABAA receptor β2 and β3 subunits as related to stress-induced hyperalgesia. Results from Western blot and immunofluorescence assays showed that c-fos protein increased in the dorsal horn of the lumbar spinal cord and GABAA receptor β2 and β3 subunit proteins decreased significantly at 6 h after exposure to 1 h of acute restraint stress. Finally, the effects of spinal GABAA receptor alteration on SIH were evaluated. These results showed that intrathecal administration of muscimol inhibited hyperalgesia induced by stress while bicuculline enhanced hyperalgesia in the control groups. Taken together, the present data reveal that GABAA receptor β2 and β3 decrease following 1 h of acute restraint stress and may play a critical role in SIH.

Opposing Roles of Estradiol and Testosterone on Stress-Induced Visceral Hypersensitivity in Rats

“…On the one hand, stress increases pain sensitivity by reducing inhibitory tone in the spinal cord (i.e. through decreasing GABA receptor function 66, 91 or inhibitory glutamate receptor activity 18 ). On the other hand, an increase in excitatory glutamate receptor activity has been reported following stress 91 .…”

Acute restraint stress regulates brain DNMT3a and promotes defensive behaviors in male rats

“…For example, a single 6-hour episode of physical restraint promoted increased tail-flick latency in rats [ 45 ], and similarly, 6 min of exposure to the forced-swim test was associated with increased analgesic responses in the tail-flick test [ 46 ]. On the other hand, rats submitted to 1-hour restraint showed hyperalgesia, observed in the tail-flick test, 6 h after the stress exposure [ 47 ]. Finally, the systemic administration of a CRF antagonist was shown to reduce visceral pain in rats [ 48 ].…”

Nitric Oxide in the Spinal Cord Is Involved in the Hyperalgesia Induced by Tetrahydrobiopterin in Chronic Restraint Stress Rats

“…Several mechanisms have been demonstrated to explain the hyperalgesia induced by chronic stress, including opioid, gamma-aminobutyric acid (GABA), glutamate, monoamine, endocannabinoid, sympathetic adrenomedullary systems, and the hypothalamic-pituitary-adrenal (HPA) axis (Jennings et al, 2014). For instance, the decrease of GABA release and GABAreceptor activation in the spinal cord involves forced swimming SIH and pain-induced c-Fos overexpression (Suarez-Roca et al, 2008;Quintero et al, 2011;Ma et al, 2014). The switch of endogenous opioid signaling from an antinociceptive to a pronociceptive pathway involves chronic SIH (Ferdousi and Finn, 2018).…”