Proceedings of The Physiological Society
University of Cambridge (2008) Proc Physiol Soc 11, PC113
Two unrelated subjects with ‘congenital’ analgesia, retention of innocuous somatic cutaneous sensations and hyperhidrosis
D. Bowsher1, F. Rice2, C. Wood3
1. Pain Research Institute, Liverpool, United Kingdom. 2. Centre for Neuropharmacology & Neuroscience, Albany Medical College, Albany, New York, USA. 3. Department of Medical Genetics, University of Cambridge, Cambridge, United Kingdom.
Subject 1 (who has one sister) was born in 1968, and suffered many childhood injuries, including fractures to his left arm such that he now has peripheral motor and sensory nerve damage in this appendage, and spinal scoliosis. He sweats unconscionably. Subject 2 was born in 1923, one of 5 siblings; painlessness was noted from childhood onwards. Neither subject has any family history of “congenital” analgesia. Both subjects have hyperhidrosis, with a skin production 3-8 greater than normal..Pharmacological manipulation in Subject 1 (stellate ganglion block, hyoscine) failed to influence the hyperhidrosis, and neither did hyoscine in Subject 2. Both had normal tactile and sharpness thresholds, and only slightly elevated vibration and innocuous thermal thresholds in comparison to normal controls. No nerve fibres could be detected in sural nerve biopsies in subject 1; and in subject 2, sural biopsy showed the C:Aδ:Aβ ratio to be 33: 6.5: 1 (270 myelinated, 178 unmyelinatd), compared with a normal ratio of 21:3:1 (4628 myelinated, 22427 unmyelinated; Jacobs and Love, 1985). Genetic analysis of Subject 1 showed no change in gene SCN9A, thus ruling out channelopathy-associated insensitivity to pain. Punch biopsies of skin in Subject 1 showed that nerve supply to the cutaneous vasculature, sweat glands and pilo-erector muscles was mostly intact, whereas virtually all of the other cutaneous innervation was absent or severely depleted, including all types of C, Aδ and Aβ-fiber endings. Importantly, the results revealed a previously unknown cholinergic innervation to the resistance arteries and arteriovenous shunts in the hand, which was also seen in normal subjects. These results suggest that humans may use their vascular afferents for purposes of conscious, albeit reduced, non-noxious somatic sensation.
Where applicable, experiments conform with Society ethical requirements