The Sprouting of High-Threshold Cutaneous Nerves and its Acceleration by Neural Activity

Abstract

<p>Previous studies have shown that in the rat the sprouting of low-threshold ("touch''-sensitive) nerves into adjacent denervated skin can occur only during a brief "critical period" of post-natal life that ends at about 20 d of age. Additionally, for any segmental nerve this sprouting occurred only in the region of that nerve's sensory dermatome. One objective of my thesis was to examine whether the sprouting of high-threshold ("pain"-sensitive) cutaneous nerves is also temporally and spatially constrained.</p> <p>The presence of high-threshold nerve endings in skin was detected behaviourally by pinching with toothed forceps; normally this elicits a reflex contraction of an underlying skeletal muscle, causing visible skin puckering. Denervated skin failed to respond in this way for the first 2-3 weeks after nerve section, but then a gradual recovery of the response occurred spreading from the adjacent innervated region of skin progressively further into the deprived area. That this recovery was due to sprouting was shown by histological examination of skin, and the findings of nerve fibres within the dermis in sensitive but not insensitive skin. The sprouting occurred in the adult animal, and proceeded beyond the dermatome border of a nerve, showing that intact high-threshold nerves are not under any obvious spatial and temporal constraints.</p> <p>During the examination for the presence of high-threshold nerve sprouting I noted that repeated skin pinching apparently accelerated the return of high-threshold sensitivity. The second main objective of the thesis was to examine what this phenomenon depended upon. In animals that were repeatedly stimulated physiologically every 4 d, all of the denervated skin became reinnervated by 20 d, compared to the 40 d or more needed for unstimulated animals. The accelerating affect was mimicked by direct electrical excitation of the remaining nerve. The results revealed that it was the latency for sprouting that was affected; once begun, the rate of sprouting was normal. The effects of electrical stimulation of the intact nerve were prevented if TTX was applied so as to block impulses proceeding centrally from the site of electrical stimulation, but not if they were only prevented from proceeding peripherally. A hypothetical mechanism to explain the effects of impulse activity in causing acceleration of sprouting is provided.</p>