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Pain Dec 2017
Review
Topics: Afferent Pathways; Animals; Humans; Hyperalgesia; Neural Inhibition; Spinal Cord
PubMed: 28885453
DOI: 10.1097/j.pain.0000000000001055 -
Pain Feb 2015
Review
Topics: Animals; Humans; Hyperalgesia; Nerve Net; Peripheral Nerves; Spinal Nerves
PubMed: 25599442
DOI: 10.1097/01.j.pain.0000460818.62406.38 -
Scandinavian Journal of Pain Jul 2022Mechanisms of complex regional pain syndrome (CRPS) are still debated. Identifying subgroups of patients have been attempted in the hope of linking clinical findings to...
OBJECTIVES
Mechanisms of complex regional pain syndrome (CRPS) are still debated. Identifying subgroups of patients have been attempted in the hope of linking clinical findings to possible mechanisms. The aim of the present study was to investigate whether subgroups of CRPS (based on quantitative sensory testing (QST)-results) differed with respect to different characteristics of pain like spontaneous ongoing or paroxysmal pain and mechanical dynamic allodynia.
METHODS
61 CRPS-patients (type 1 and 2) were examined clinically and with QST, in affected and contralateral extremity, with assessment of thresholds for warmth, cold and heat-and cold pain.
RESULTS
43 patients (20 men, 23 men) were diagnosed with CRPS 1 (70.5%) and 18 patients (8 women and 10 men) with CRPS 2 (29.5%). Three subgroups were defined based on thermal thresholds; A (thermal allodynia 22.9%), B (thermal hyposensitivity 37.3%), C (thermal allodynia and hyposensitivity 39.3%). Paroxysmal pain was more prevalent in patients with thermal allodynia (merging group A + C, 25/38-65.8%) compared to patients without thermal allodynia (group B, 5/23-21.7%) (p-value=0.00085).
CONCLUSIONS
We suggest that cold allodynia is based on hyper-excitability of very superficial skin nociceptors. The correlation between paroxysmal pain, allodynia to light touch and cold allodynia suggests that activity in those peripheral nociceptors can drive both, paroxysmal pain and spinal sensitization leading to stroke evoked allodynia. Mechanistically, the physical cold stimulus can unmask disease-related hyperexcitability by closure of temperature-sensitive potassium channels or induction of resurgent currents. Small fiber degeneration alone may not be the crucial mechanism in CRPS, nor explain pain.
Topics: Cold Temperature; Complex Regional Pain Syndromes; Female; Humans; Hyperalgesia; Male; Pain; Reflex Sympathetic Dystrophy
PubMed: 35429156
DOI: 10.1515/sjpain-2021-0208 -
Journal of Neural Transmission (Vienna,... Apr 2020The dorsal horns of the spinal cord and the trigeminal nuclei in the brainstem contain neuron populations that are critical to process sensory information. Neurons in... (Review)
Review
The dorsal horns of the spinal cord and the trigeminal nuclei in the brainstem contain neuron populations that are critical to process sensory information. Neurons in these areas are highly heterogeneous in their morphology, molecular phenotype and intrinsic properties, making it difficult to identify functionally distinct cell populations, and to determine how these are engaged in pathophysiological conditions. There is a growing consensus concerning the classification of neuron populations, based on transcriptomic and transductomic analyses of the dorsal horn. These approaches have led to the discovery of several molecularly defined cell types that have been implicated in cutaneous mechanical allodynia, a highly prevalent and difficult-to-treat symptom of chronic pain, in which touch becomes painful. The main objective of this review is to provide a contemporary view of dorsal horn neuronal populations, and describe recent advances in our understanding of on how they participate in cutaneous mechanical allodynia.
Topics: Animals; Chronic Pain; Hyperalgesia; Inflammation; Neuralgia; Posterior Horn Cells
PubMed: 32239353
DOI: 10.1007/s00702-020-02159-1 -
Neurology(R) Neuroimmunology &... Nov 2023Neuropathic pain is common and distressing. Improved mechanistic understanding and pharmacotherapies are urgently needed. Molecularly specific pain syndromes may provide...
OBJECTIVES
Neuropathic pain is common and distressing. Improved mechanistic understanding and pharmacotherapies are urgently needed. Molecularly specific pain syndromes may provide insights with translational relevance. Glycine receptors are known to play a key role in inhibitory neurotransmission in the spinal dorsal horn and have therefore been considered as targets for analgesic development. While autoantibodies directed against glycine receptors may rarely arise spontaneously in humans, a detailed phenotype of neuropathic pain and allodynia in association with these autoantibodies has not been described.
METHODS
We describe the case of a previously well adult presenting with severe neuropathic pain and allodynia as part of an autoimmune brainstem and spinal syndrome with glycine receptor autoantibodies.
RESULTS
Our patient experienced a severe illness, including marked neuropathic pain and allodynia, hypoventilation, tetraparesis, and ophthalmoplegia. A diagnosis of progressive encephalomyelitis with rigidity and myoclonus was made. Neuropathic pain was characterized with validated instruments and responded promptly to cause-directed immunotherapy.
DISCUSSION
A detailed longitudinal phenotyping, using validated pain measurement instruments, of severe neuropathic pain and allodynia associated with likely pathogenic glycine receptor autoantibodies is reported. This case may have relevance for translational development of analgesics targeting glycinergic neurotransmission.
Topics: Adult; Humans; Receptors, Glycine; Hyperalgesia; Neuralgia; Autoantibodies; Immunotherapy
PubMed: 37640544
DOI: 10.1212/NXI.0000000000200160 -
Science Translational Medicine Oct 2018The brush of a feather and a pinprick are perceived as distinct sensations because they are detected by discrete cutaneous sensory neurons. Inflammation or nerve injury...
The brush of a feather and a pinprick are perceived as distinct sensations because they are detected by discrete cutaneous sensory neurons. Inflammation or nerve injury can disrupt this sensory coding and result in maladaptive pain states, including mechanical allodynia, the development of pain in response to innocuous touch. However, the molecular mechanisms underlying the alteration of mechanical sensitization are poorly understood. In mice and humans, loss of mechanically activated PIEZO2 channels results in the inability to sense discriminative touch. However, the role of Piezo2 in acute and sensitized mechanical pain is not well defined. Here, we showed that optogenetic activation of -expressing sensory neurons induced nociception in mice. Mice lacking in caudal sensory neurons had impaired nocifensive responses to mechanical stimuli. Consistently, ex vivo recordings in skin-nerve preparations from these mice showed diminished Aδ-nociceptor and C-fiber firing in response to mechanical stimulation. Punctate and dynamic allodynia in response to capsaicin-induced inflammation and spared nerve injury was absent in Piezo2-deficient mice. These results indicate that Piezo2 mediates inflammation- and nerve injury-induced sensitized mechanical pain, and suggest that targeting PIEZO2 might be an effective strategy for treating mechanical allodynia.
Topics: Action Potentials; Animals; Behavior, Animal; Capsaicin; Hyperalgesia; Ion Channels; Mechanotransduction, Cellular; Mice, Knockout; Neurons; Nociception; Nociceptors; Pain
PubMed: 30305457
DOI: 10.1126/scitranslmed.aat9897 -
Current Pain and Headache Reports Jun 2006Migraine is a common disorder that often is accompanied by cutaneous allodynia. Cutaneous allodynia on the head has been linked to sensitization of neurons in the... (Review)
Review
Migraine is a common disorder that often is accompanied by cutaneous allodynia. Cutaneous allodynia on the head has been linked to sensitization of neurons in the trigeminal nucleus caudalis in animal models of migraine. In addition, migraine with allodynia is refractory to acute treatment with triptans. Understanding the mechanisms of allodynia, preventing its development, and finding effective treatments have become a priority in headache research. This paper reviews recent research on the pathogenesis of headache and the generation of allodynia. We discuss the regions of the nervous system that are involved in generating and maintaining headache pain and allodynia. We also discuss recent advances in the treatment of migraine based on translation research.
Topics: Analgesics; Animals; Drug Resistance; Humans; Hyperalgesia; Migraine Disorders
PubMed: 18778578
DOI: 10.1007/s11916-006-0050-y -
The Journal of Headache and Pain Feb 2019Administration of endogenous mediators or exogenous chemicals in migraine patients provoke early headaches and delayed migraine-like attacks. Although migraine provoking...
BACKGROUND
Administration of endogenous mediators or exogenous chemicals in migraine patients provoke early headaches and delayed migraine-like attacks. Although migraine provoking substances are normally vasodilators, dilation of arterial vessels does not seem to be the sole contributing factor, and the underlying mechanisms of the delayed migraine pain are mostly unknown. Sustained mechanical allodynia is a common response associated with the local administration of various proalgesic substances in experimental animals and humans. Here, we investigated the ability of a series of endogenous mediators which provoke or do not provoke migraine in patients, to cause or not cause mechanical allodynia upon their injection in the mouse periorbital area.
METHODS
Mechanical allodynia was assessed with the von Frey filament assay. Stimuli were given by subcutaneous injection in the periorbital area of C57BL/6J mice; antagonists were administered by local and systemic injections.
RESULTS
Calcitonin gene related peptide (CGRP), but not adrenomedullin and amylin, pituitary adenylyl cyclase activating peptide (PACAP), but not vasoactive intestinal polypeptide (VIP), histamine, prostaglandin E (PGE) and prostacyclin (PGI), but not PGF evoked a dose-dependent periorbital mechanical allodynia. The painful responses were attenuated by systemic or local (periorbital) administration of antagonists for CGRP (CLR/RAMP1), PACAP (PAC-1), histamine H, PGE (EP), and PGI (IP) receptors, respectively.
CONCLUSIONS
The correspondence between substances that provoke (CGRP; PACAP, histamine, PGE, PGI), or do not provoke (VIP and PGF), migraine-like attacks in patients and periorbital allodynia in mice suggests that the study of allodynia in mice may provide information on the proalgesic mechanisms of migraine-provoking agents in humans. Results underline the ability of migraine-provoking substances to initiate mechanical allodynia by acting on peripheral terminals of trigeminal afferents.
Topics: Animals; Calcitonin Gene-Related Peptide; Disease Models, Animal; Hyperalgesia; Mice; Mice, Inbred C57BL; Migraine Disorders; Nociception; Receptor Activity-Modifying Protein 1; Vasodilator Agents
PubMed: 30764776
DOI: 10.1186/s10194-019-0968-1 -
The Journal of Family Practice Apr 2022► Nausea ►Paresthesia ► Cold allodynia.
► Nausea ►Paresthesia ► Cold allodynia.
Topics: Female; Humans; Hyperalgesia; Nausea; Paresthesia
PubMed: 35561236
DOI: 10.12788/jfp.0376 -
Cephalalgia : An International Journal... Mar 2023Migraine is a complex neurological disorder involving generalized abnormalities in processing sensory information. Adopting evidence that central sensitization imposes... (Clinical Trial)
Clinical Trial
Pre-treatment non-ictal cephalic allodynia identifies responders to prophylactic treatment of chronic and episodic migraine patients with galcanezumab: A prospective quantitative sensory testing study (NCT04271202).
BACKGROUND
Migraine is a complex neurological disorder involving generalized abnormalities in processing sensory information. Adopting evidence that central sensitization imposes major hurdles in the treatment of migraine, we hypothesized that it is the non-ictal (rather than ictal) allodynia that may determine the outcome of migraine prevention with peripherally-acting drugs.
METHODS
To test this hypothesis, we used Quantitative Sensory Testing to determine whether it is possible to identify a patient's response to prophylactic treatment with galcanezumab based on presence/absence of cephalic and/or extracephalic allodynia during the pre-treatment non-ictal phase of migraine.
RESULTS
Using strict criteria for allodynia (heat 32-40°C, cold 32-20°C, mechanical <60 g), we report that (a) the incidence of pre-treatment non-ictal cephalic allodynia was 21% in the 24 responders (>50% decrease in monthly migraine days) and 85% in the 19 non-responders; (b) the incidence of non-ictal extracephalic allodynia distinguishes responders from non-responders less accurately; and that (c) the incidence of non-ictal cephalic allodynia was similar in the chronic migraine and high-frequency episodic migraine groups.
CONCLUSIONS
Clinically, the findings suggest that presence/absence of non-ictal allodynia can be used to identify galcanezumab responders with nearly 80% accuracy and galcanezumab non-responders with nearly 85% accuracy. Mechanistically, the presence of non-ictal allodynia (reflecting a state of activity-independent central sensitization) in both chronic migraine and high-frequency episodic migraine patients raises the possibility that the state of non-ictal allodynia may be attributed to physiological properties of central trigeminovascular neurons that are due to the genetic load of the individual patient rather than their migraine frequency.
Topics: Humans; Antibodies, Monoclonal, Humanized; Double-Blind Method; Hyperalgesia; Migraine Disorders; Prospective Studies; Treatment Outcome
PubMed: 36786278
DOI: 10.1177/03331024221147881