Experimental Evidence on the Nature of Cutaneous Hyperalgesia

Hardy, James D.; Wolff, Harold G.; Goodell, Helen

doi:10.1172/jci102227

Cited by 245 publications

(97 citation statements)

References 20 publications

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“…Like previous studies that employed thermal stimuli at or below the heat-pain threshold (Hardy et al 1950;Raja et al 1984;LaMotte et al 1991;Kilo et al 1994;Ali et al 1996), neither the warmth nor heat-pain threshold differed between sites of secondary mechanical hyperalgesia and control sites in the present study. However, in certain circumstances hyperalgesia to heat appears to develop after a delay in the zone of secondary mechanical hyperalgesia (e.g., Sumikura et al 2003Sumikura et al , 2005.…”

Section: Discussionsupporting

confidence: 43%

Topically applied capsaicin inhibits sensitivity to touch but not to warmth or heat-pain in the region of secondary mechanical hyperalgesia

Drummond

Blockey

2009

Somatosensory & Motor Research

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The aim of this study was to investigate tactile sensitivity near the site of primary hyperalgesia evoked by capsaicin applied topically to the dorsolateral aspect of the hand. In the first experiment (N = 15), touch thresholds increased in the fifth finger ipsilateral to the topically applied capsaicin, but remained unchanged at greater distances from the site of capsaicin treatment. In a second experiment (N = 12), the effect of the capsaicin treatment on sensations evoked not only by light touch but also by warmth, heat-pain, and pressure-pain to a 2-mm diameter steel probe was investigated in the fifth finger. Again, tactile sensitivity was inhibited at the fifth finger, even though stimulation with a cotton bud evoked no discomfort; moreover, sensitivity to warmth and heat-pain were unimpaired. However, sensitivity to pressure-pain increased in the fifth finger after the capsaicin treatment, possibly due to activation of nociceptors sandwiched between the probe tip and bone that normally responded to sharp stimuli. These findings suggest that the central mechanisms that mediate secondary mechanical hyperalgesia suppress sensitivity to innocuous tactile sensations. This effect may contribute to tactile hypoesthesia in chronic pain conditions.

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Section: Discussionsupporting

confidence: 43%

Topically applied capsaicin inhibits sensitivity to touch but not to warmth or heat-pain in the region of secondary mechanical hyperalgesia

Drummond

Blockey

2009

Somatosensory & Motor Research

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“…In addition, these changes are responsible for the misperception of pain in response to non-noxious stimuli -termed allodynia. 42 Primary hyperalgesia is explained by sensitization of peripheral nociceptors, [44][45][46] while secondary hyperalgesia may be caused by altered CNS processing of mechanoreceptor impulses from peripheral tissues. 45,[47][48][49][50] Clinical pain may be divided into two entities: inflammatory pain, which is the consequence of trauma to peripheral tissues (i.e., surgical incision, dissection, burns, etc); and neuropathic pain, which is the result of direct injury to nervous tissue (i.e., nerve transection).…”

Section: Mechanisms Of Hypersensitivitymentioning

confidence: 99%

Preemptive analgesia I: physiological pathways and pharmacological modalities

Kelly

Ahmad

Brull

2001

Can J Anesth/J Can Anesth

259

181

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P Pu ur rp po os se e: : This two-part review summarizes the current knowledge of physiological mechanisms, pharmacological modalities and controversial issues surrounding preemptive analgesia.S So ou ur rc ce e: : Articles from 1966 to present were obtained from the MEDLINE databases. Search terms included: analgesia, preemptive; neurotransmitters; pain, postoperative; hyperalgesia; sensitization, central nervous system; pathways, nociception; anesthetic techniques; analgesics, agents.P Pr ri in nc ci ip pa al l f fi in nd di in ng gs s: : The physiological basis of preemptive analgesia is complex and involves modification of the pain pathways. The pharmacological modalities available may modify the physiological responses at various levels. Effective preemptive analgesic techniques require multi-modal interception of nociceptive input, increasing threshold for nociception, and blocking or decreasing nociceptor receptor activation. Although the literature is controversial regarding the effectiveness of preemptive analgesia, some general recommendations can be helpful in guiding clinical care. Regional anesthesia induced prior to surgical trauma and continued well into the postoperative period is effective in attenuating peripheral and central sensitization. Pharmacologic agents such as NSAIDs (non-steroidal anti-inflammatory drugs) opioids, and NMDA (Nmethyl-D-aspartate) -and alpha-2-receptor antagonists, especially when used in combination, act synergistically to decrease postoperative pain.C Co on nc cl lu us si io on n: : The variable patient characteristics and timing of preemptive analgesia in relation to surgical noxious input requires individualization of the technique(s) chosen. Multi-modal analgesic techniques appear most effective.Objectif : La présente revue, en deux parties, résume les connaissances actuelles sur les mécanismes physiologiques et les modalités pharmacologiques de lanalgésie préventive ainsi que sur les questions controversées qui lentourent.Sources : Des articles, de 1966 à aujourdhui, obtenus à partir des bases de données MEDLINE. Les termes de la recherche compren-

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“…A fter skin injury, an increased sensitivity to mechanical stimuli occurs in a large, uninjured area surrounding the injury site (1,2). This phenomenon is termed secondary hyperalgesia and is the consequence of neuroplastic changes leading to a state of sensitization of the central nervous system (central sensitization) (3).…”

mentioning

confidence: 99%

Pharmacological modulation of pain-related brain activity during normal and central sensitization states in humans

Iannetti

Zambreanu

Wise

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

250

207

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Abnormal processing of somatosensory inputs in the central nervous system (central sensitization) is the mechanism accounting for the enhanced pain sensitivity in the skin surrounding tissue injury (secondary hyperalgesia). Secondary hyperalgesia shares clinical characteristics with neurogenic hyperalgesia in patients with neuropathic pain. Abnormal brain responses to somatosensory stimuli have been found in patients with hyperalgesia as well as in normal subjects during experimental central sensitization. The aim of this study was to assess the effects of gabapentin, a drug effective in neuropathic pain patients, on brain processing of nociceptive information in normal and central sensitization states. Using functional magnetic resonance imaging (fMRI) in normal volunteers, we studied the gabapentin-induced modulation of brain activity in response to nociceptive mechanical stimulation of normal skin and capsaicin-induced secondary hyperalgesia. The dose of gabapentin was 1,800 mg per os, in a single administration. We found that (i) gabapentin reduced the activations in the bilateral operculoinsular cortex, independently of the presence of central sensitization; (ii) gabapentin reduced the activation in the brainstem, only during central sensitization; (iii) gabapentin suppressed stimulus-induced deactivations, only during central sensitization; this effect was more robust than the effect on brain activation. The observed drug-induced effects were not due to changes in the baseline fMRI signal. These findings indicate that gabapentin has a measurable antinociceptive effect and a stronger antihyperalgesic effect most evident in the brain areas undergoing deactivation, thus supporting the concept that gabapentin is more effective in modulating nociceptive transmission when central sensitization is present.deactivation ͉ fMRI ͉ hyperalgesia ͉ nociceptive system A fter skin injury, an increased sensitivity to mechanical stimuli occurs in a large, uninjured area surrounding the injury site (1, 2). This phenomenon is termed secondary hyperalgesia and is the consequence of neuroplastic changes leading to a state of sensitization of the central nervous system (central sensitization) (3). Secondary hyperalgesia can be experimentally induced by treating the skin with high doses of the vanilloid capsaicin (by intradermal injection or topical application).Two forms of mechanical hyperalgesia occur in the area of secondary hyperalgesia: hyperalgesia to gentle skin stroking (stroking hyperalgesia or allodynia) and hyperalgesia to punctate stimuli (punctate hyperalgesia). Although both stroking and punctate hyperalgesia are due to central sensitization, they have different psychophysical characteristics (punctate hyperalgesia is easier to establish, it encompasses a larger area and it is longer-lasting than stroking hyperalgesia). They are mediated by different primary afferents (3): stroking hyperalgesia is signaled by low-threshold mechanoreceptors (4), whereas punctate hyperalgesia is signaled by capsaicin-insensitive A-fi...

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Experimental Evidence on the Nature of Cutaneous Hyperalgesia

Cited by 245 publications

References 20 publications

Topically applied capsaicin inhibits sensitivity to touch but not to warmth or heat-pain in the region of secondary mechanical hyperalgesia

Topically applied capsaicin inhibits sensitivity to touch but not to warmth or heat-pain in the region of secondary mechanical hyperalgesia

Preemptive analgesia I: physiological pathways and pharmacological modalities

Pharmacological modulation of pain-related brain activity during normal and central sensitization states in humans

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