Low-threshold unmyelinated mechanoreceptors : a novel substrate of allodynia in human skin

Abstract

The human hairy skin is innervated by a very ancient system of slow-conducting low-threshold mechanoreceptors termed C-tactile fibres (CTs). Intriguingly, even the existence of CTs in the distal limbs (non-hairy/glabrous skin) remains to be established, let alone their functional significance in the neural system. In this thesis, we examined the function of CTs through the prism of pain and its multifarious expressions, in particular touch-evoked pain (allodynia). In Paper I, we showed that the deep somatic pain generated by infusion of hypertonic saline (HS: 5%) into the tibialis anterior muscle is enhanced by concurrent application of vibration (200 Hz- 200 ++m) and brushing (1.0 and 3.0 cm s-1) to the overlying hairy skin. In Paper II, we demonstrated that a comparable expression of allodynia elicits when vibration and brushing are applied across skin types and spinal segments - glabrous skin of fingers and hairy skin of dorsal forearm - during HS-infusion into the flexor carpi ulnaris muscle. In Paper III, we showed that vibration evokes pain/allodynia following eccentric exercise-induced muscle soreness (no resting pain). Furthermore, a cognate expression of touch-evoked allodynia was observed in a clinical subject with activity-triggered heel-pain without exposure to eccentric exercise. In Paper IV, we demonstrated that, in the presence of HS-induced cutaneous pain, the application of vibration to an adjacent region of skin generates allodynia. In all four papers, the vibration- and brush-evoked allodynia persisted following conduction block of myelinated afferents by compression. In contrast, the effect was abolished during conduction block of cutaneous C fibres by injecting a local anaesthetic into the skin stimulation by vibration. Collectively these psychophysical observations provide the first human evidence that CTs arising from hairy skin, and their functional counterparts in glabrous skin, contribute to mechanical allodynia. This phenomenon appears to be reproducible in perceptible (HS-induced), imperceptible (exercise-induced) and pathological pain-states.

Date of Award	2012
Original language	English