Itch is transmitted to the spinal cord dorsal horn by small diameter C and Aδ fibers responding to pruritogens like histamine [2]. These first order neurons synapse onto second order spinothalamic projection neurons that ascend to the thalamus and cortex to generate the sensation of itch [3][4].

Scratching initiation involves spinal interneurons that form part of local reflex circuits [5]. These interneurons receive input from low threshold mechanoreceptors when the skin is contacted during a scratching movement [6]. They activate motor neurons innervating limb muscles to produce a scratching motion, providing rapid reflexive initiation of scratching before slower pathways fully process the itch stimulus [1].

Higher centers like the periaqueductal gray matter further contribute to persistent scratching once initiated,

The periaqueductal gray (PAG) matter receives strong inputs from regions involved in processing awareness, emotion, and nociception, including the hypothalamus, frontal and insular cortices, amygdala, and spinal cord [1]. This allows the PAG to integrate sensory, affective, and cognitive factors involved in the itch-scratch cycle. Through downstream projections to raphe nuclei activating descending inhibitory pathways, the PAG can modulate activity in dorsal horn itch transmission neurons [1][2].

Persistent scratching elicits damaging mechanical stimulation, further activating pruriceptive pathways. The PAG can prolong scratching by attenuating this nociceptive input through its descending modulation over spinal processing [3]. Reduced nociception enables extended scratching without triggering withdrawal. The PAG also receives higher input from regions involved in motivation and reward [1], which may positively reinforce persistent scratching.

Sources:

1-3. Goldstein, E. B. (Ed.). (2015). Encyclopedia of perception. Sage Publications.

4, 6. Mason, P. (2011). Medical neurobiology. Oxford University Press.

5. Hains, B.C. (2009). Pain. Chelsea House Publishers.