Pain in the ultrafast lane

The textbook view is that pain in humans is signaled at a slower speed than touch.

Conduction speed is important for several downstream processes and critical in clinical testing to assess nerve function.

We have discovered that the pain pathway in humans is not limited to slowly conducting thinly myelinated and unmyelinated primary afferent neurons (nociceptors) but is also equipped with thickly myelinated (Aβ) neurons.

These ultrafast nociceptors (UFNs) are insensitive to gentle touch, encode painful skin indentations, and have a conduction velocity similar to Aβ touch neurons.

Here, we propose to study the physiology and molecular makeup of UFNs and elucidate their role in peripheral and spinal pain mechanisms.

We will combine single-unit in vivo electrophysiology with psychophysics and optical imaging to compare nerve function with behavior and skin reactivity to acute inflammation.

The effect of inflammation on UFN responses will be compared between healthy individuals and rare patients with a selective ion-channel mutation to identify the underlying molecular pathway for pain-hypersensitivity.

The ultrafast component of the protective pain withdrawal reflex will be studied, and a technique developed to test UFN function in the clinic.

The identification of UFNs is of broad scientific interest and will provide clinicians, neuroscientists, and pharmaceutical companies new ways to diagnose pain and may ultimately yield a new therapeutic target for chronic pain.