Selective expression of opsins in nociceptive neurons in the sciatic nerve of mice

Neuromodulation techniques offer drug-free management of chronic pain. However, electrical stimulation does not discriminate between sensory and motor fibres, nor between their functional subtypes, and can therefore result in off-target effects (e.g., motor activation). One way to alter nociceptive fibre activity alone is through the selective expression of light sensitive opsins within nociceptive fibres. Thus, light may be used to alter nociceptive activity whilst leaving neighbouring fibres unaffected. We selectively expressed either excitatory (channelrhodopsin; ChR2) or inhibitory (halorhodopsin; NpHR) light-gated ion channels/pumps in nociceptive fibres in the sciatic nerve of mice. AAV6-hSyn-ChR2(H134R)-mCherry or AAV6-hSyn-NpHR-EYFP was injected into the sciatic nerve of adult mice. Four weeks later, compound action potentials were recorded in the sciatic nerve in vivo to assess optical excitation or inhibition of electrically evoked nociceptor activity. Sciatic nerve injections resulted in ChR2 or NpHR expression in cell bodies and axons of a subset of cells in the dorsal root ganglia. Expression was selective for small diameter nociceptor neurons. Blue light applied to the sciatic nerve (expressing ChR2) produced selective activation of slow fibres (conduction velocity = 0.4m/s), whereas electrical stimulation recruited both fast and slow fibres. Yellow light stimulation of the sciatic nerve (expressing NpHR) altered electrically evoked nerve responses, by increasing the threshold for slow fibre activity. With selective expression of excitatory and inhibitory opsins in nociceptors and a reliable method for evoking nociceptor activity in the sciatic nerve, this study provides the foundation to test light-mediated modulation of nociceptive activity in the peripheral nervous system.