Stimuli-evoked NOergic molecules and neuropeptides at acupuncture points and the gracile nucleus contribute to signal transduction of propagated sensation along the meridian through the dorsal medulla-thalamic pathways

Numerous studies from different international groups have demonstrated that sensations can be propagated along acupuncture channel pathways.The propagated sensation along the channel pathway(PSCP)can be elicited by electroacupuncture(EA),transcutaneous electrical nerve stimulation(TENS),manual acupuncture(MA),and heat applied to distal acupuncture points(acupoints).Nitric oxide(NO)levels were reported to be elevated in the gracile nucleus and skin regions near to the EA sites,with higher levels at acupoints associated with an enhanced expression of NO synthase and transient receptor potential vanilloid type 1.The stimuli,EA,MA,TENS,and heat,have been used to elicit axonal reflexes,which increase local release of NO and neuropeptides such as calcitonin gene related peptide.Furthermore,the sensation of PSCP along the body surface occurs only ipsilaterally to the stimulated acupoints in various human studies,which does not support the involvement of the spinal-thalamic pathway,which would involve cross over transmission of the signals.The gracile nucleus receives ascending input from the sciatic nerve and responds to somatosensory stimulation mainly on the ipsilateral side via the dorsal column pathway.EA at Zusanli(ST36)increases NO release and expression of NO synthase mainly in the ipsilateral side of the gracile nucleus,while the cardiovascular effects and analgesic responses to EA at ST36 are changed by influences of l-arginine-derived NO synthesis in the ipsilateral gracile nucleus in rats.The stimuli-induced release of NOergic molecules and neuropeptides exist high levels in the acupoints,which contain rich neuronal components and blood vessels.Enhanced NOergic molecules at acupoints cause axon reflexes during the stimuli,which elevate cutaneous blood flow.Elevated NOergic molecules and local blood flow may spread over acupoints one after another along the meridian lines differing from nerve pathways following the stimuli to induce PSCP.The same types of stimulation also elicit NO release in the gracile nucleus,which contributes to the somatosensory signal transduction of PSCP through the dorsal medulla-thalamic pathways.Other substances such as serotonin and catecholamines are proposed to mediate responses and certain effects of acupuncture-like stimulation but their mechanisms are poorly-understood.In this review we summarize the current understanding of the neurobiological processes of PSCP research with an emphasis on recent developments of NO mediating stimulation-evoked axon reflexes and somatosensory signal transduction for PSCP perceptions through the dorsal medulla-thalamic pathways.