Why Pain During Wound Healing May be a Good Sign

Amazing stuff!

"... In a new study, scientists found that neuron endings grow into injured skin and muscle tissue and communicate with immune cells through a neuropeptide to promote tissue healing. These findings, published in Nature, provide insights on how neurons enable healing and open up potential therapeutic targets for regenerative tissue healing strategies.  ..."

From the abstract:

"The immune system has a critical role in orchestrating tissue healing. As a result, regenerative strategies that control immune components have proved effective. This is particularly relevant when immune dysregulation that results from conditions such as diabetes or advanced age impairs tissue healing following injury. Nociceptive sensory neurons have a crucial role as immunoregulators and exert both protective and harmful effects depending on the context. However, how neuro–immune interactions affect tissue repair and regeneration following acute injury is unclear. Here we show that ablation of the NaV1.8 nociceptor impairs skin wound repair and muscle regeneration after acute tissue injury. Nociceptor endings grow into injured skin and muscle tissues and signal to immune cells through the neuropeptide calcitonin gene-related peptide (CGRP) during the healing process. CGRP acts via receptor activity-modifying protein 1 (RAMP1) on neutrophils, monocytes and macrophages to inhibit recruitment, accelerate death, enhance efferocytosis and polarize macrophages towards a pro-repair phenotype. The effects of CGRP on neutrophils and macrophages are mediated via thrombospondin-1 release and its subsequent autocrine and/or paracrine effects. In mice without nociceptors and diabetic mice with peripheral neuropathies, delivery of an engineered version of CGRP accelerated wound healing and promoted muscle regeneration. Harnessing neuro–immune interactions has potential to treat non-healing tissues in which dysregulated neuro–immune interactions impair tissue healing."

Why Pain During Wound Healing May be a Good Sign | The Scientist Magazine® "Sensory neurons grow into injured tissues and modulate the immune system to promote healing."

Wound healing is a billion dollar drain on the health system – this discovery hopes to plug it (original news release)

CGRP sensory neurons promote tissue healing via neutrophils and macrophages

Fig. 1: NaV1.8+ nociceptors that express CGRP mediate tissue healing via myeloid cells.

Neuron endings extend into tissues undergoing repair and influence immune cell function. A neuron ending cluster (red) surrounded by immune cells (yellow/orange) in an injured muscle.