Activation of the cortical pain network by soft tactile stimulation after injection of sumatriptan
ABSTRACT The anti-migraine drug sumatriptan often induces unpleasant somatosensory side effects, including a dislike of being touched. With a double-blind cross-over design, we studied the effects of sumatriptan and saline on perception (visual analogue scale) and cortical processing (functional magnetic resonance imaging) of tactile stimulation in healthy subjects. Soft brush stroking on the calf (n=6) was less pleasant (p<0.04) and evoked less activation of posterior insular cortex in the sumatriptan compared to the saline condition. Soft brushing activated pain processing regions (anterior insular, lateral orbitofrontal, and anterior cingulate cortices, and medial thalamus) only in the sumatriptan condition, whereas activation of somatosensory cortices was similar in both conditions. Soft brush stroking on the palm (n=6) was equally pleasant in both conditions. One possible mechanism for the activation of pain processing regions by brush stroking is sensitization of nociceptors by sumatriptan. Another possibility is inhibition of a recently discovered system of low-threshold unmyelinated tactile (CT) afferents that are present in hairy skin only, project to posterior insular cortex, and serve affective aspects of tactile sensation. An inhibition of impulse transmission in the CT system by sumatriptan could disinhibit nociceptive signalling and make light touch less pleasant. This latter alternative is consistent with the observed reduction in posterior insular cortex activation and the selective effects of stimulation on hairy compared to glabrous skin, which are not explained by the nociceptor sensitization account.
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- "anterior insula for integration (Olausson et al., 2002; Craig, 2003; Bjornsdotter et al., 2009; Loken et al., 2009; Paulus and Stein, 2010; McGlone et al., 2012) contributing to an overall awareness of the body's condition by providing signals of the experienced sensation (Craig, 2002; Naqvi and Bechara, 2009; Paulus et al., 2009; Bjornsdotter et al., 2010). Although CT afferents mainly provide hedonic information, Aβ afferents can also produce a pleasant sensation as demonstrated by a soft brush stroke on the palm, in an area where CT afferents are lacking (Kramer et al., 2007). In addition, Aβ afferents have been shown to activate insular connections to regions of orbitofrontal cortex involved in emotional evaluation (Olausson et al., 2010). "
ABSTRACT: Tactile interactions with our environment stimulate afferent fibers within the skin, which deliver information about sensations of pain, texture, itch and other feelings to the brain as a comprehensive sense of self. These tactile interactions can stimulate brain regions involved in interoception and reward processing. This study examined subjective, behavioral, and neural processing as a function of age during stimulation of A-beta (Aβ) and C tactile (CT) afferents using a soft brush stroke task. 16 adolescents (ages 15-17), 22 young adults (ages 20-28), and 20 mature adults (ages 29-55) underwent a simple continuous performance task while periodically anticipating and experiencing a soft touch to the palm or forearm, during functional magnetic resonance imaging (fMRI). fMRI results showed that adolescents displayed greater bilateral posterior insula activation than young and mature adults across all conditions and stimulus types. Adolescents also demonstrated greater bilateral posterior insula activation than young and mature adults specifically in response to the soft touch condition. Adolescents also exhibited greater activation than mature adults in bilateral inferior frontal gyrus and striatum during the soft touch condition. However, mature adults showed greater striatum activation than adolescents and young adults during anticipation. In the left anterior cingulate cortex, mature adults exhibited greater activation than adolescents and young adults when anticipating the upcoming touch. These results support the hypothesis that adolescents show an exaggerated neural response to pleasant stimulation of afferents, which may have profound effects on how they approach or avoid social and risky situations. In particular, heightened interoceptive reactivity to pleasant stimuli might cause adolescents to seek experiences that are associated with pleasant stimulation.Frontiers in Behavioral Neuroscience 02/2014; 8:52. DOI:10.3389/fnbeh.2014.00052 · 3.27 Impact Factor
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- "However, cortical activation evoked by a neutral tactile stimulus predominantly activates the discriminative-cognitive areas, the primary and secondary somatosensory cortices. It has been argued that the tactile allodynia experienced following administration of sumatriptan may be explained by an induced deficit in affective (pleasant) processing (Krämer et al. 2007). In contrast, our results strongly indicate that CT activation can mediate a crossover to the affective component of touch, i.e. neutral to painful. "
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. Abstract We 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 subjects reported vibration and brushing as non-painful (VAS = 0). These results demonstrate that CT fibres in hairy skin mediate allodynia, and that CT-mediated inputs have a pluripotent central effect.The Journal of Physiology 08/2011; 589(Pt 16):4065-75. DOI:10.1113/jphysiol.2011.211326 · 5.04 Impact Factor
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- "For example, CT afferents have partly similar projections as nociceptive afferents in the central nervous system, and CT afferents have been shown to reduce nociceptive signaling at the level of lamina II of the dorsal root in rats (Lu and Perl, 2003). Tactile allodynia may be a consequence of CT inhibition (Krä mer et al., 2007; Linde et al., 2004), and CT stimulation is effective in reducing experimental pain (Krä mer et al., 2006). These observations suggest that stimulating or preserving CT function may be an important future strategy in the treatment of chronic pain. "
ABSTRACT: CT (C tactile) afferents are a distinct type of unmyelinated, low-threshold mechanoreceptive units existing in the hairy but not glabrous skin of humans and other mammals. Evidence from patients lacking myelinated tactile afferents indicates that signaling in these fibers activate the insular cortex. Since this system is poor in encoding discriminative aspects of touch, but well-suited to encoding slow, gentle touch, CT fibers in hairy skin may be part of a system for processing pleasant and socially relevant aspects of touch. CT fiber activation may also have a role in pain inhibition. This review outlines the growing evidence for unique properties and pathways of CT afferents.Neuroscience & Biobehavioral Reviews 11/2008; 34(2):185-91. DOI:10.1016/j.neubiorev.2008.09.011 · 8.80 Impact Factor