Transient receptor potential channel A1 involved in calcitonin gene-related peptide release in neurons

Transient receptor potential channel A1 is one of the important transducers of noxious stimuli in the primary afferents, which may contribute to generation of neurogenic inflammation and hyperalgesia. The present study was designed to investigate if activation of transient receptor potential channel A1 may induce calcitonin gene-related peptide release from the primary afferent neurons. We found that application of allyl isothiocyanate, a transient receptor potential channel A1 activator, caused calcitonin gene-related peptide release from the cultured rat dorsal root ganglion neurons. Knock- down of transient receptor potential channel A1 with an antisense oligodeoxynucleotide prevented calcitonin gene-related peptide release by allyl isothiocyanate application in cultured dorsal root ganglion neurons. Thus, we concluded that transient receptor potential channel A1 activation caused calcitonin gene-related peptide release in sensory neurons.

Possible implications of animal models for the assessment of visceral pain

Acute pain,provoked generally after the activation of peripheral nociceptors,is an adaptive sensory function that alerts the individual to avoid noxious stimuli.However,uncontrolled acute pain has a maladaptive role in sensory activity leading to development of a chronic pain state which persists even after the damage is resolved,or in some cases,in the absence of an initial local acute injury.Huge numbers of people suffer from visceral pain at least once during their life span,leading to substantial health care costs.Although studies reporting on the mechanism of visceral pain are accumulating,it is still not precisely understood.Therefore,this review aims to elucidate the mechanism of visceral pain through an evaluation of different animal models and their application to develop novel therapeutic approaches for treating visceral pain.To assess the nociceptive responses in viscera,several visceral pain models such as inflammatory,traction,stress and genetic models utilizing different methods of measurement have been devised.Among them,the inflammatory and traction models are widely used for studying the visceral pain mechanism of different disease conditions and post-operative surgery in humans and animals.A hapten,2,4,6-trinitrobenzene sulfonic acid(TNBS),has been extensively used as an inflammatory agent to induce visceral pain.The traction model seems to cause a strong pain stimulation and autonomic reaction and could thus be the most appropriate model for studying the underlying visceral pain mechanism and for probing the therapeutic efficacies of various anesthetic and analgesics for the treatment of visceral pain and hyperalgesia.