Silencing of spinal Trpv1 attenuates neuropathic pain in rats by inhibiting CAMKII expression and ERK2 phosphorylation

Abstract

Accumulating evidence suggests a potential role of transient receptor potential vanilloid 1 (TRPV1) channels in inflammatory and cancer-related pain. However, the role of TRPV1 in the maintenance of neuropathic pain remains elusive. The current study investigated the effects of transient Trpv1 gene silencing using a small interference RNA (siRNA) on neuropathic pain induced by chronic constriction injury (CCI) of the sciatic nerve in rats. Seven days after CCI, the TRPV1 siRNA was intrathecally administered (5 µg/15 µl, once daily for 2 days). TRPV1 and Ca 2+ /calmodulin-dependent protein kinase II (CAMKII) expression and extracellular signal-regulated kinase (ERK) phosphorylation in the spinal cord were detected using western blotting. The thresholds to mechanical and thermal stimuli were determined before and after intrathecal TRPV1 siRNA administration. TRPV1 and CAMKII expression and ERK2 phosphorylation in the spinal cord were upregulated after CCI. Intrathecal administration of the TRPV1 siRNA not only attenuated behavioural hyperalgesia but also reduced the expression of TRPV1 and CAMKII, as well as ERK2 phosphorylation. Based on these results, silencing of the TRPV1 gene in the spinal cord attenuates the maintenance of neuropathic pain by inhibiting CAMKII/ERK2 activation and suggests that TRPV1 represents a potential target in pain therapy.

Antiallodynic effect of PhAR‐DBH‐Me involves cannabinoid and TRPV1 receptors

“…Recent reports suggest that neuropathic pain increases TRPV1 expression, as well as the Ca 2+ /calmodulin‐dependent protein kinase II (CAMKII) and extracellular signal‐regulated kinase (ERK) phosphorylation. These data confirm that there is a up phosphorylation (sensitization) of TRPV1 receptors on neuropathic condition 59 . In line with this, one of the acute desensitization theories suggest that protein kinase C (PKC) phosphorylates or sensitizes TRPV1 receptors; this sensitization occurs when the receptor is binding to analogues as capsaicin.…”

Alterations in Anandamide Synthesis and Degradation during Osteoarthritis Progression in an Animal Model

“…Guo et al showed an increase in CAMKII, TRPV1 and pERK1/2 protein levels in the spinal dorsal horn of animals suffering from chronic pain. Moreover, silencing of the TRPV1 gene attenuated mechanical and thermal hyperalgesia and CaMKII and ERK2 phosphorylation [ 25 ]. On the other hand, CaMKII is required for TRPV1 ligand binding.…”

“…The degree of pain does not always correlate with the extent of joint damage or presence of active inflammation, we investigated the occurrence of a central component of OA pain by correlating OA pain behavior of the animals reported in the previous studies [ 24 ] with the assessment of ATF-3, a marker of spinal neuronal activity. Involvement of mitogen-activated protein kinases 3 and 14 (MAPK3 and MAPK14, respectively) in the chronic pain formation has been shown in preclinical studies [ 25 , 26 ]. Furthermore, the present investigation aimed to examine the spinal and joint endocannabinoid systems in combination with TRPV1 and its sensitization factors during pain development in a rat sodium monoiodoacetate (MIA) model of OA.…”

A novel approach for detection of functional expression of TRPV1 channels on regenerated neurons following nerve injury

“…In contrast, in a spinal nerve ligation model, TRPV1 mRNA expression increased in DRG neurons up to 4 weeks after injury [13]. A study on chronic constriction injuries of the sciatic nerve reported increased TRPV1 protein in the spinal dorsal horn and DRG 1 week after injury [48]. Another study using a chronic constrictive spinal nerve injury model reported increased TRPV1 protein in the spinal cord at 1 and 2 weeks after injury [14].…”