Fast-conducting mechanoreceptors contribute to withdrawal behavior in normal and nerve injured rats

Danilo Boada M., Martin T.J., Peters C.M., Hayashida K., Harris M.H., Houle T.T., Boyden E.S., Eisenach J.C., Ririe D.G. (2014) Fast Conducting Mechanoreceptors Contribute to Withdrawal Behavior in Normal and Nerve Injured Rats, Pain 155(12):2646-2655.

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Fast-conducting myelinated high-threshold mechanoreceptors (AHTMR) are largely thought to

transmit acute nociception from the periphery. However, their roles in normal withdrawal and

in nerve injury–induced hyperalgesia are less well accepted. Modulation of this subpopulation

of peripheral neurons would help define their roles in withdrawal behaviors. The optically

active proton pump, ArchT, was placed in an adeno-associated virus-type 8 viral vector with

the CAG promoter and was administered by intrathecal injection resulting in expression in

myelinated neurons. Optical inhibition of peripheral neurons at the soma and transcutaneously

was possible in the neurons expressing ArchT, but not in neurons from control animals.

Receptive field characteristics and electrophysiology determined that inhibition was neuronal

subtype–specific with only AHTMR neurons being inhibited. One week after nerve injury the

AHTMR are hyperexcitable, but can still be inhibited at the soma and transcutaneously.

Withdrawal thresholds to mechanical stimuli in normal and in hyperalgesic nerve-injured

animals also were increased by transcutaneous light to the affected hindpaw. This suggests

that AHTMR neurons play a role not only in threshold-related withdrawal behavior in the

normal animal, but also in sensitized states after nerve injury. This is the first time this

subpopulation of neurons has been reversibly modulated to test their contribution to

withdrawal-related behaviors before and after nerve injury. This technique may prove useful

to define the role of selective neuronal populations in different pain states.


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