Corticosterone Mediates Reciprocal Changes in CB 1 and TRPV1 Receptors in Primary Sensory Neurons in the Chronically Stressed Rat

Abstract

Background & Aims Chronic stress is associated with visceral hyperalgesia in functional gastrointestinal disorders. We investigated whether corticosterone plays a role in chronic psychological stress-induced visceral hyperalgesia. Methods Male rats were subjected to 1-hour water avoidance (WA) stress or subcutaneous corticosterone injection daily for 10 consecutive days in the presence or absence of corticoid receptor antagonist RU-486 and cannabinoid receptor agonist WIN55,212-2. The visceromotor response (VMR) to colorectal distension (CRD) was measured. Receptor protein levels were measured and whole-cell patch-clamp recordings employed to assess TRPV1 currents in L6-S2 DRG neurons. Mass spectrometry was used to measure endocannabinoid anandamide content. Results Chronic WA stress was associated with visceral hyperalgesia in response to CRD, increased stool output and reciprocal changes in CB1 (decreased) and TRPV1 (increased) receptor expression and function. Treatment of WA stressed rats with RU-486 prevented these changes. Control rats treated with serial injections of corticosterone in situ demonstrated a significant increase in serum corticosterone associated with visceral hyperalgesia, enhanced anandamide content, increased TRPV1 and decreased CB1 receptor protein levels which were prevented by co-treatment with RU-486. Exposure of isolated control L6-S2 DRGs in vitro to corticosterone reproduced the changes in CB1 and TRPV1 receptors observed in situ which was prevented by co-treatment with RU-486 or WIN55,212-2. Conclusions These results support a novel role for corticosterone to modulate CB1 and TRPV1 receptor pathways in L6-S2 DRGs in the chronic WA stressed rat which contributes to visceral hyperalgesia observed in this model.

Iron overload causes osteoporosis in thalassemia major patients through interaction with transient receptor potential vanilloid type 1 (TRPV1) channels

“…45 Moreover, exposure to a variety of challenges may profoundly alter CB1 and CB2 gene expression and mRNA levels. 22,30,40,46,47 Given the potential anti-osteoporotic effects of TRPV1 pharmacological stimulation/desensitization, 22 we treated osteoclasts from TM patients with the TRPV1 agonist resiniferatoxin, which led to an increase in CB2 receptor expression and a dramatic reduction of cathepsin K ( Figure 3). This occurred in the absence of any significant change in TRAP mRNA levels ( Figure 3A).…”

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“…Abdelhamid et al reported the involvement of CRF2 receptors in musculoskeletal hyperalgesia in mice exposed to forced swim stress . Chronic subcutaneous administration of corticosterone to rats produced visceral hyperalgesia, as measured by colorectal distension (Hong et al, 2011). Furthermore, chronic water avoidance induces changes in transient receptor potential receptor TRPV1 and the cannabinoid (CB 1 ) receptor expression in the spinal cord (Hong et al, 2009, Hong et al, 2011 which were attenuated by the glucocorticoid receptor antagonist (RU-486).…”

“…Chronic subcutaneous administration of corticosterone to rats produced visceral hyperalgesia, as measured by colorectal distension (Hong et al, 2011). Furthermore, chronic water avoidance induces changes in transient receptor potential receptor TRPV1 and the cannabinoid (CB 1 ) receptor expression in the spinal cord (Hong et al, 2009, Hong et al, 2011 which were attenuated by the glucocorticoid receptor antagonist (RU-486). The results were consistent with previous work from Fereidoni et al where adrenalectomy diminished forced swim stress-induced hyperalgesia in rats (Fereidoni et al, 2007).…”

“…Another study suggested that subcutaneous injection of corticosterone in situ showed a significant increase in serum corticosterone associated with visceral hyperalgesia by altering the TRPV1/CB 1 receptor expression (Hong et al, 2011). Recently, it has been demonstrated that chronic stress induces visceral and somatosensory hyperalgesia that is associated with differential changes in endovanilloid levels in DRG innervating the pelvic viscera and lower extremities.…”

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“…There is also evidence for the involvement of GR and MR in the development of pain-like behaviors induced by a repeated stress. Systemic MIFE administration reversed colonic hypersensitivity to colorectal distension in response to either a repeated water avoidance stress or subcutaneous CORT injections, with a potential mechanism of altering cannabinoid receptor (CB) type 1 and transient receptor potential cation channel V1 receptors in the dorsal horn of the spinal cord (Hong et al, 2011). In a similar fashion, MIFE or SPIRO administered to the CeA also prevented repeated water avoidance stress-induced pain-like behaviors (Myers and Greenwood-Van Meerveld, 2012).…”