<p>Neuroimaging Of Cold Allodynia Reveals A Central Disinhibition Mechanism Of Pain</p>

Abstract

PurposeAllodynia refers to pain evoked by physiologically innocuous stimuli. It is a disabling symptom of neuropathic pain following a lesion within the peripheral or central nervous system. In fact, two different pathophysiological mechanisms of cold allodynia (ie, hypersensitivity to innocuous cold) have been proposed. The peripheral sensitization of nociceptive neurons can produce cold allodynia, which can be induced experimentally by a topical application of menthol. An alternative mechanism involves reduced inhibition of central pain processing by innocuous cold stimuli. A model to induce the latter type of allodynia is the conduction block of peripheral A-fiber input.Patients and methodsIn the presented study, functional MRI was used to analyze these two different experimental models of cold allodynia. In order to identify the underlying cerebral activation patterns of both mechanisms, the application of menthol and the induction of a mechanical A-fiber blockade were studied in healthy volunteers.ResultsThe block-induced cold allodynia caused significantly stronger activation of the medial polymodal pain processing pathway, including left medial thalamus, anterior cingulate cortex, and medial prefrontal cortex. In contrast, menthol-induced cold allodynia caused significantly stronger activity of the left lateral thalamus as well as the primary and secondary somatosensory cortices, key structures of the lateral discriminative pathway of pain processing. Mean pain intensity did not differ between both forms of cold allodynia.ConclusionExperimental cold allodynia is mediated in different cerebral areas depending on the underlying pathophysiology. The activity pattern associated with block-induced allodynia confirms a fundamental integration between painful and non-painful temperature sensation, ie, the cold-induced inhibition of cold pain.

Aβ-CT affective touch: Touch pleasantness ratings for gentle stroking and deep pressure exhibit dependence on A-fibers

“…We initiated a nerve compression block over the left superficial radial nerve following validated procedures[26, 32, 33]: while the left hand rested in semi-prone position, a ∼1-inch cloth tourniquet was placed over the left forearm about 7cm from the wrist. A 5-lb weight was dangled from the tourniquet, similar to the weights used in some nerve compression studies[27] (see Figure 2 ).…”

“…This technique often takes an hour to achieve loss of touch and cold perception[33], but does not affect major blood vessels or induce significant pain[28]. The block was released within a common safety time window of 90min for healthy research participants[26].…”

“…The Brushing Rating Task, Pressure Rating Task, and Baseline Nerve Function Tasks were each conducted a second time to provide familiarization and comfort with the tasks prior to nerve block placement. Nerve Block Placement: We initiated a nerve compression block over the left superficial radial nerve following validated procedures [26,32,33]: while the left hand rested in semi-prone position, a ~1-inch cloth tourniquet was placed over the left forearm about 7cm from the wrist. A 5-lb weight was dangled from the tourniquet, similar to the weights used in some nerve compression studies [27] (see Figure 2).…”

“…Ischemic nerve block yields clear separation of A-and C-fiber functions [25] for a large area of skin, but cause more pain and discomfort. Nerve compression blocks affect a smaller skin surface area, but with minimal discomfort-and have been used previously to correlate specific nerve afferents with sensory percepts [26][27][28]. Furthermore, the latter technique has demonstrated preferential blockade of A-fibers during microneurography recordings in humans [29,30].…”

The role of TRPM8 in the pathophysiology of migraine

“…3 TRPM8 is involved in menthol-induced cold allodynia, a condition that activates the left lateral thalamus and the primary and secondary somatosensory cortices, which are related to pain processing. 4 TRPM8 induces cold allodynia and, at the same time, it is necessary for cooling/menthol-based analgesia. 2 Regarding migraine, it is equally curious that cold temperatures can trigger a migraine attack, while menthol can cause pain relief.…”