Relief of itch by scratching: state-dependent inhibition of primate spinothalamic tract neurons

Abstract

Itch is relieved by scratching, but the neural mechanisms that are responsible for this are unknown. Spinothalamic tract (STT) neurons respond to itch-producing agents and transmit pruritic information to the brain. We observed that scratching the cutaneous receptive field of primate STT neurons produced inhibition during histamine-evoked activity but not during spontaneous activity or activity evoked by a painful stimulus, suggesting that scratching inhibits the transmission of itch in the spinal cord in a state-dependent manner.Itch is an unpleasant sensation that is associated with the desire to scratch. For most itches, relief is obtained by scratching in or around the region of itchy skin. However, itch that is coincident with skin disease or systemic disorders can be severe. In these circumstances, the desire to scratch is often overwhelming, but incessant scratching is harmful and leads to itch-scratch cycles that damage the skin and exacerbate the problem 1 . The mechanism by which scratching sup-presses itch is unknown. However, it has been hypothesized that this mechanism occurs in the CNS because noxious counterstimuli (for example, scratching) reduce itch when delivered many centimeters away from the site of itching and itch does not develop in a zone of cutaneous centrally mediated allodynia 2-5. Histamine-sensitive dorsal horn neurons with unidentified projections are variably depressed by counterstimuli in rats6; however, unlike monkeys7, rats do not scratch in response to histamine, complicating the interpretation of these data with regard to itch.In humans, anterolateral cordotomy eliminates the perception of itch from contralateral body sites below the lesion, implicating the STT in the transmission of pruritic information to the brain 8 . STT neurons can be activated for many minutes following the cutaneous application of itch-producing agents such as histamine 9-11 , matching the sensation of itch in humans 12 . Therefore, we examined whether the responses to histamine in primate STT neurons could be inhibited by scratching in the receptive field. STT neurons were recorded in the lumbar dorsal horn and were identified by antidromic stimulation (Supplementary Methods and Supplementary Fig. 1 Every neuron tested had a mechanically sensitive receptive field and was excited by scratching (n = 28). Repeated scratches to the receptive field of single STT neurons reliably evoked similar discharges (Fig. 1). Two-thirds of STT neurons showed an after-discharge following scratching (Fig. 1b).Histamine (20 μg in 10 μL) was then injected intradermally into the receptive field. In eight neurons that responded to histamine ( Supplementary Fig. 2 online), the receptive field was scratched for 10 s during the response. Each histamine-responsive neuron showed fewer action potentials during the 10-s period immediately following the scratch than during the 10-s period before the scratch (Fig. 2). Most neurons increased their discharge during scratching, but two cells appeared to reduce their discharge ...

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