Regarding the distinct role of the amygdala in anxiety-like behaviors21 and the anxiogenic effect of TRPV1 receptors,22,23 it may be suggested that reduced TRPV1 mRNA in the amygdala but not in the hippocampus partly mediates morphine-induced anxiolysis.24 In accordance, previous studies have shown the existence of a functional
and complex interaction between opioid and TRPV1 receptors. For example, capsaicin-induced thermal allodynia is attenuated by stimulating MOR opioid receptors in the central nervous system of rhesus monkeys.25 On the other hand, it has been reported that SB366791 Inhibitors,research,lifescience,medical and capsazepine as TRPV1 receptor antagonists suppress analgesic tolerance and physical dependence to morphine10,26 and the development of tolerance to morphine is substantially attenuated in the absence of TRPV1-expressing primary afferent neurons of the RTX-treated rats.27 In a very recent study, Spahn and colleagues have demonstrated that TRPV1 activity increased in DRG neurons during morphine Inhibitors,research,lifescience,medical withdrawal syndrome.28Although the authors did not evaluate the role of central Inhibitors,research,lifescience,medical TRPV1 receptors, they have concluded that change in TRPV1 activity during opioid withdrawal syndrome is a new selleckchem Trichostatin A mechanism that contributes to opioid withdrawal-induced hyperalgesia. In contrast, it has been reported that capsaicin and the MOR receptor agonist, DAMGO, when co-administered into the ventrolateral-periaqueductal
gray at non-analgesic doses Inhibitors,research,lifescience,medical per se induce analgesic effects29 and capsaicin can inhibit some morphine withdrawal symptoms in rats.30 The mechanism by which opioids affect TRPV1 receptors may be divided into rapid and delayed effects. Opioids via Gi/o proteins in a cAMP/PKA-selleck kinase inhibitor dependent pathway decrease translocation and multimerization of TRPV1 channels from an intracellular store of inactive TRPV1 monomers in the membranes of target cells.31 This effect has been suggested as a cellular
mechanism for rapid and fine tuning of TRPV1 responses independent of transcriptional changes. This suggestion was further Inhibitors,research,lifescience,medical supported by the ability of opioids to inhibit capsaicin responses potentiated by cAMP-dependent PKA.32 The results of a study by Spahn has also shown that activation of TRPV1 receptors Dacomitinib during opioid withdrawal is cAMP dependent and mediated through activation of protein kinase A.28Therefore, opioids by inhibition of protein kinase A rapidly modulate TRPV1 receptor activity. The delayed effects of opioids may be presented by changes in TRPV1 receptor transcription and/or translation. For example, it has been reported that TRPV1 mRNA increased in the spinal cord and sciatic nerve (2.7 and 3.9 fold, respectively) and decreased in the DRG of morphine-treated rats.10 This finding in conjunction with the results of the present study suggests that change in TRPV1 mRNA level during morphine dependence is target dependent.