Dose-dependent pain and mechanical hyperalgesia in humans after intradermal injection of capsaicin

Simone, Donald A.; Baumann, Thomas; LaMotte, Robert H.

doi:10.1016/0304-3959(89)90079-1

Cited by 461 publications

(306 citation statements)

References 14 publications

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“…The data indicated that acute inflammation with IS resulted in a decrease in the PWL and PWT in the behavioral studies and this is consistent with previous studies using acute inflammatory mediators (Taiwo et al, 1987;Taiwo et al, 1989;Simone et al, 1989b;Gilchrist et al, 1996). Sensitization to heat was confirmed at the single fiber level, with CMH units showing a decrease in threshold and an increase in discharge rate in response to IS.…”

Section: Differences In Mechanisms Underlying Thermal Vs Mechanical Ssupporting

confidence: 90%

Group II metabotropic glutamate receptor activation attenuates peripheral sensitization in inflammatory states

Zhou

Carlton

2008

Neuroscience

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Several lines of evidence indicate that Group II metabotropic glutamate receptor (mGluR) activation can depress sensory transmission. We have reported the expression of Group II mGluRs on unmyelinated axons, many of which were presumed to be nociceptors, in the rat digital nerve (Carlton et al., 2001b). The goals of the present study are to further our understanding of Group II modulation of nociceptor processing in the periphery, documenting behavioral changes using inflammatory models and documenting, for the first time, cutaneous single fiber activity following exposure to a Group II agonist (2R,4R)-4-aminopyrrolidine-2,4-dicarboxylate (APDC) and antagonist LY341495 (LY). The data indicate that peripheral Group II mGluR activation does not depress nociceptive behaviors or nociceptor fiber responses in the non-sensitized state (i.e. following brief nociceptive mechanical or thermal stimulation) but can depress these responses when nociceptors are sensitized by exposure to formalin or inflammatory soup. Group II mGluR agonist-induced inhibition can be blocked by a selective Group II antagonist. Peripheral Group II mGluR-induced inhibition evoked in these studies occurs through activation of local receptors and not through spinal or supraspinal mechanisms. The data indicate that administration of selective Group II agonists may be potent therapeutic agents for prevention of peripheral sensitization and for treatment of inflammatory pain. KeywordsGroup II mGluR; pain; APDC; LY341495; formalin; inflammation; inflammatory soup Glutamate and glutamate receptors play an important role in peripheral pain mechanisms in animals (Carlton, 2001;Carlton et al., 2003) and humans (McNearney et al., 1999;McNearney et al., 2000;Cairns et al., 2001;Alfredson et al., 2001;Alfredson and Lorentzon, 2002;Svensson et al., 2003;Cairns et al., 2003). To date, ionotropic glutamate receptors (iGluRs) including N-methyl-D-aspartate (NMDA) and non-NMDA receptors are implicated in peripheral cutaneous pain mechanisms Bleakman et al., 2006).More recent studies indicate that metabotropic glutamate receptors (mGluRs) can modulate peripheral nociceptor function. In contrast to iGluRs, which are ligand-gated ion channel receptors, mGluRs mediate their function via G-protein coupled receptors which trigger Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access Author ManuscriptNeuroscience. Author manuscript; available in PMC 2009 June 23. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript intracellular second-messenger systems (Pin and Duvoisin, 1995). Accordin...

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Section: Differences In Mechanisms Underlying Thermal Vs Mechanical Ssupporting

confidence: 90%

Group II metabotropic glutamate receptor activation attenuates peripheral sensitization in inflammatory states

Zhou

Carlton

2008

Neuroscience

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“…If we applied stimulus intensities of ϳ80 mA (20), most of these mechanoinsensitive fibers would be excited (23). In this case, the flare would become at least as large as after application of capsaicin (24). However, such high stimuli intensities cannot be used for routine clinical testing.…”

Section: Discussionmentioning

confidence: 99%

Electrically Stimulated Axon Reflexes Are Diminished in Diabetic Small Fiber Neuropathies

et al. 2004

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Axon reflex mediated flare depends on the density and the function of cutaneous C-fibers and may be impaired in diabetic neuropathy. We induced neurogenic axon reflex flare by intracutaneous electrical stimulation and analyzed size and intensity of the flare on the dorsum of the foot and ventral thigh with laser Doppler imaging (LDI). We investigated 12 diabetic subjects with small fiber neuropathies (SFNs), 5 diabetic subjects without neuropathy (NO-Ns), and 14 healthy control subjects. Five of the normal subjects were reassessed after 12 months. In comparing patients with SFN to control subjects, we found that SFN flare size but not the intensity of vasodilation (flux) was reduced on the feet (P < 0.001) and thighs (P < 0.007). Furthermore, electrical thresholds for flare induction were increased (thighs P < 0.001 and feet P < 0.03). In NO-Ns, flare size at the feet (P < 0.02) and flux at both sites (thighs P < 0.001 and feet P < 0.002) were even increased. Test/ retest evaluation of our method revealed a good correlation (r ‫؍‬ 0.83, P < 0.004). Intracutaneous electrical stimulation of C-fibers and scanning the flare with LDI is a sensitive tool to reliably detect small fiber impairment in diabetic SFN subjects and even increased neuropeptide release in NO-Ns. Diabetes 53:769 -774, 2004 S mall fiber neuropathy (SFN) is a common complication in diabetes and other disorders. Clinical features of this disease often include pain and dysesthesia such as burning feet and neurovascular abnormalities (1). Despite its high incidence and clinical importance, there are only a few methods to quantify peripheral small fiber dysfunction. These include quantitative sensory testing (2), analysis of heart rate variability, assessment of sudomotor axon reflexes (3), or skin biopsies (4). However, availability of these procedures in clinical routine is limited and sensitivity of the psychophysical methods may be questioned.Analysis of axon reflexes is a simple and specific test for peripheral C-fiber function. Activation of nociceptive Cfibers in the skin by mechanical (5) or chemical stimuli (6,7) induces a spreading vasodilation, which is visible as a "flare response" surrounding the injured site (8). The flare depends on both the density and function of C-fiber nociceptors in the skin, in particular the subgroup of mechanoinsensitive "silent" nociceptors (9). The neuronal pathway of neurogenic vasodilation is organized as an axon reflex. Activation of peripheral C-nociceptors provokes nerve impulses, which are conducted centrally. At some branching points of the axonal tree these action potentials may invade peripheral branches (10), causing the release of vasodilatory neuropeptides from skin nerve terminals, e.g., calcitonin gene-related peptide and substance P (11,12).In previous studies, quantitative analysis of vasodilation in axon reflex flares (flare intensity) employing single channel laser Doppler flowmetry (5,13) was not sensitive enough to reliably distinguish between control subjects and patients with mild to mode...

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“…Intradermal injection of capsaicin, a main ingredient from hot chili peppers, elicits a strong acute pain accompanied by a multitude of sensory abnormalities including hyperalgesia (more pain to noxious stimuli) and allodynia [233,234] . Hence, Iadarola et al [235] designed experiments to image regional brain activity in normal volunteers during capsaicin-induced intense pain and mechanical allodynia by using the PET H 2 15 O-bolus method.…”

Section: Abnormal Pain Processing In the Hfmentioning

confidence: 99%

Roles of the hippocampal formation in pain information processing

2009

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Abstract:Pain is a complex experience consisting of sensory-discriminative, affective-motivational, and cognitive-evaluative dimensions. Now it has been gradually known that noxious information is processed by a widely-distributed, hierarchicallyinterconnected neural network, referred to as neuromatrix, in the brain. Thus, identifying the multiple neural networks subserving these functional aspects and harnessing this knowledge to manipulate the pain response in new and beneficial ways are challenging tasks. Albeit with elaborate research efforts on the cortical responses to painful stimuli or clinical pain, involvement of the hippocampal formation (HF) in pain is still a matter of controversy. Here, we integrate previous animal and human studies from the viewpoint of HF and pain, sequentially representing anatomical, behavioral, electrophysiological, molecular/ biochemical and functional imaging evidence supporting the role of HF in pain processing. At last, we further expound on the relationship between pain and memory and present some unresolved issues.

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Dose-dependent pain and mechanical hyperalgesia in humans after intradermal injection of capsaicin

Cited by 461 publications

References 14 publications

Group II metabotropic glutamate receptor activation attenuates peripheral sensitization in inflammatory states

Group II metabotropic glutamate receptor activation attenuates peripheral sensitization in inflammatory states

Electrically Stimulated Axon Reflexes Are Diminished in Diabetic Small Fiber Neuropathies

Roles of the hippocampal formation in pain information processing

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