Allodynia mediated by C‐tactile afferents in human hairy skin

Abstract

Non-technical summary What triggers a realignment of sensations, e.g. a stimulus that is perceived as non-painful in intact skin, but evokes pain in sunburned skin, is yet to be ascertained. This phenomenon is clinically termed allodynia. We show that gentle tactile stimulation (vibration and brushing) of the hairy skin can exacerbate the underlying muscle pain (allodynia) evoked by infusion of hypertonic saline into the tibialis anterior muscle. This effect is dependent upon a low-threshold, mechanosensitive class of nerve fibres in the hairy skin known as C-tactile (CT) fibres. Knowledge of the role of CT fibres in allodynia increases our understanding of the mechanisms that underlie sensory-perceptual abnormalities -a common manifestation of clinical-pain states and neurological disorders. AbstractWe recently showed a contribution of low-threshold cutaneous mechanoreceptors to vibration-evoked changes in the perception of muscle pain. Neutral-touch stimulation (vibration) of the hairy skin during underlying muscle pain evoked an overall increase in pain intensity, i.e. allodynia. This effect appeared to be dependent upon cutaneous afferents, as allodynia was abolished by intradermal anaesthesia. However, it remains unclear whether allodynia results from activation of a single class of cutaneous afferents or the convergence of inputs from multiple classes. Intriguingly, no existing human study has examined the contribution of C-tactile (CT) afferents to allodynia. Detailed psychophysical observations were made in 29 healthy subjects (18 males and 11 females). Sustained muscle pain was induced by infusing hypertonic saline (HS: 5%) into tibialis anterior muscle (TA). Sinusoidal vibration (200 Hz-200 μm) was applied to the hairy skin overlying TA. Pain ratings were recorded using a visual analogue scale (VAS). In order to evaluate the role of myelinated and unmyelinated cutaneous afferents in the expression of vibration-evoked allodynia, compression block of the sciatic nerve, and low-dose intradermal anaesthesia (Xylocaine 0.25%) were used, respectively. In addition, the modulation of muscle pain by gentle brushing (1.0 and 3.0 cm s −1 ) -known to excite CT fibres -was examined. Brushing stimuli were applied to the hairy skin with all fibres intact and following the blockade of myelinated afferents. During tonic muscle pain (VAS 4-6), vibration evoked a significant and reproducible increase in muscle pain (allodynia) that persisted following compression of myelinated afferents. During compression block, the sense of vibration was abolished, but the vibration-evoked allodynia persisted. In contrast, selective anaesthesia of unmyelinated cutaneous afferents abolished the allodynia, whereas the percept of vibration remained unaffected. Furthermore, allodynia was preserved in the adjacent non-anaesthetized skin. Conformingly, gentle brushing produced allodynia (at both brushing speeds) that persisted during the blockade of myelinated afferents. Prior to the induction and following cessation of muscle pain, all subj...

Hairy Sensation

“…Hence, the reduction in pain behavior in VGLUT3 mutant mice may also result from functional deficits in the brain that are independent from VGLUT3 expression in C-LTMRs. A recent study in humans suggests that C-tactile afferents mediate mechanical allodynia that accompanies experimentally induced muscle pain (54). Muscle pain was induced by infusing hypotonic saline into the muscle, and allodynia in the hairy skin overlying the muscle was evoked with a vibrotactile stimulus.…”

Peripheral afferents and spinal inhibitory system in dynamic and static mechanical allodynia

“…Although there are Aδ/C low-threshold mechanoreceptors functioning as light touch sensors in the hairy skin, their exact role in mechanical allodynia in humans remains unclear [29; 38]. …”

C-tactile afferents: Cutaneous mediators of oxytocin release during affiliative tactile interactions?

“…However other studies have reported continued allodynia following large fibre blockade, but relief by local anaesthetization of c-fibers in patients experiencing ongoing pain. Using a novel 'two-compartment model' of allodynia Nagi et al (2011) induced pain by infusion of hypertonic saline into the tibialis anterior muscle, whereas the neutral stimulus (vibration or gentle stroking) was applied to the overlying skin, physically separated from the muscle below by the underlying fascia. The authors found that both vibration and brushing evoked allodynia was dependent upon the functioning of unmyelinated cutaneous afferents, but persisted during blockade of myelinated fibers.…”