Sound-stress-induced altered nociceptive behaviors are associated with increased spinal CRFR2 gene expression in a rat model of burn injury

Abstract

Sound stress (SS) elicits behavioral changes, including pain behaviors. However, the neuronal mechanisms underlying SS-induced pain behaviors remain to be explored. The current study examined the effects of SS on nociceptive behaviors and changes in expression of the spinal corticotropin-releasing factor (CRF) system in male Sprague Dawley rats with and without thermal pain. We also studied the effects of SS on plasma corticosterone and fecal output. Rats were exposed to 3 days of SS protocol (n = 12/group). Changes in nociceptive behaviors were assessed using thermal and mechanical pain tests. Following the induction of SS, a subgroup of rats (n = 6/group) was inflicted with thermal injury and on day 14 postburn nociceptive behaviors were reassessed. Spinal CRF receptor mRNA expression was analyzed by semiquantitative reverse transcription polymerase chain reaction (RT-PCR). In addition, plasma corticosterone and spinal CRF concentrations were quantified using enzyme-linked immunosorbent assay (ELISA). Increased defecation was observed in SS rats. SS produced transient mechanical allodynia in naive rats, whereas it exacerbated thermal pain in thermally injured rats. Spinal CRFR2 mRNA expression was unaffected by stress or thermal injury alone, but their combined effect significantly increased its expression. SS had no effect on plasma corticosterone and spinal CRF protein in postburn rats. To conclude, SS is capable of exacerbating postburn thermal pain, which is linked to increased CRFR2 gene expression in the spinal cord. Future studies have to delineate whether attenuation of CRFR2 signaling at the spinal level prevents stress-induced exacerbation of burn pain.

Keywords:

• sound stress
• corticotropin-releasing factor receptor-2
• thermal injury
• corticosterone
• thermal pain
• mechanical pain

Acknowledgments

We would like to thank Dr Subrata Haldar for his valuable comments and editing this manuscript. Drs Natasha M Sosanya and Bopaiah P Cheppudira are supported by National Research Council (NRC) Associate Fellowship program. This work was supported by Congressionally Directed Medical Research Programs – Applied Pain Research (MR157005C). Dr Bopaiah P Cheppudira is the Principal Investigator of this grant.

Disclosure

The opinions or assertions contained herein are the private views of the authors and are not to be considered as official or as reflecting the views of the Department of the Army or the Department of Defense. The authors report no other conflicts of interest in this work.