A novel analgesic approach to optogenetically and specifically inhibit pain transmission using TRPV1 promoter

Traditional Chinese herbal extracts inducing autophagy as a novel approach in therapy of nonalcoholic fatty liver disease

“…), which is originally from Mexico but has become a favorite seasoning food in China. Odorless and colorless dietary capsaicin is a potent agonist of transient receptor potential vanilloid 1 (TRPV1), which is a non-selective cation channel with a preference for positive ions that transmit sensations of pain[60]. Long-term intake of dietary capsaicin can lower blood pressure, reduce cholesterol accumulations, and accelerate the decomposition and excretion of cholesterol[61,62].…”

Changing channels in pain and epilepsy: Exploiting ion channel gene therapy for disorders of neuronal hyperexcitability

“…As light of longer wavelength has greater tissue penetration [73], RSOs also permit modulation of excitability in neurons much further from an optical source, opening optogenetic stimulation up to deep and diffuse brain structures for which implantation of optical fibres may be deemed too invasive. In addition, RSOs also offer the tantalising prospect of non‐invasive transcranial optogenetics; as discussed above, proof‐of‐principle for transdermal optogenetic modulation of DRG neuron firing has already been demonstrated [52,53,74]. And finally, RSOs could permit bimodal suppression of neuronal excitability.…”

“…Although viral transduction was not specific for nociceptive neurons, subsequent optical stimulation produced an acute analgesic effect, and completely reversed the mechanical and thermal hypersensitivity experienced in a chronic sciatic nerve constriction model of neuropathic pain [52]. An acute analgesic effect has also been achieved with optogenetic inhibition of DRG neurons expressing the light‐sensitive proton pump ArchT [53]. In an attempt to selectively transduce nociceptive afferents, an AAV5 vector was designed in which the ArchT transgene was placed under the control of a transient receptor potential cation channel subfamily V member 1 (TRPV1) promoter; TRPV1 is a non‐selective cation channel preferentially expressed within nociceptive DRG neurons [54].…”

Spotlight on pain: optogenetic approaches for interrogating somatosensory circuits

“…Optical manipulations of pain behaviors have also been achieved in nontransgenic animals using AAV vectors to transduce peripheral fibers [68]. More relevant clinically, viral delivery of the inhibitory opsins halorodopsin [68] or archaerhodopsin [19,85] to peripheral sensory neurons enabled light-dependent blunting of behavioral responses to thermal and mechanical stimulation [68,85]. Optical inhibition also reversed mechanical and thermal hypersensitivity in models of neuropathic pain [19,68], suggesting a possible therapeutic option for using optogenetics in treating chronic pain.…”

“…Initial approaches relied on illumination of the hindpaw in restrained animals [73] or the exposed sciatic nerve in anesthetized transgenic mice [90]. Illumination via fiber optic cables permitted basic reflexive assays of thermal and mechanical pain, but required simultaneous illumination of the hindpaw during stimulation [40,68,85] (Fig. 2F).…”