-
The Lancet. Neurology Sep 2014Allodynia (pain due to a stimulus that does not usually provoke pain) and hyperalgesia (increased pain from a stimulus that usually provokes pain) are prominent symptoms... (Review)
Review
Allodynia (pain due to a stimulus that does not usually provoke pain) and hyperalgesia (increased pain from a stimulus that usually provokes pain) are prominent symptoms in patients with neuropathic pain. Both are seen in various peripheral neuropathies and central pain disorders, and affect 15-50% of patients with neuropathic pain. Allodynia and hyperalgesia are classified according to the sensory modality (touch, pressure, pinprick, cold, and heat) that is used to elicit the sensation. Peripheral sensitisation and maladaptive central changes contribute to the generation and maintenance of these reactions, with separate mechanisms in different subtypes of allodynia and hyperalgesia. Pain intensity and relief are important measures in clinical pain studies, but might be insufficient to capture the complexity of the pain experience. Better understanding of allodynia and hyperalgesia might provide clues to the underlying pathophysiology of neuropathic pain and, as such, they represent new or additional endpoints in pain trials.
Topics: Humans; Hyperalgesia; Neuralgia
PubMed: 25142459
DOI: 10.1016/S1474-4422(14)70102-4 -
Neurological Sciences : Official... May 2012An impaired processing of sensory afferents in the brainstem plays a key role in the development of migraine attack and for many of its clinical aspects. The repetition... (Review)
Review
An impaired processing of sensory afferents in the brainstem plays a key role in the development of migraine attack and for many of its clinical aspects. The repetition or prolonged of painful stimuli over time would be able to produce a prolonged and reversible increase of excitability and synaptic efficacy in the nociceptive pathways of the central nervous system. This phenomenon, known as sensitization, involves specifically the caudal trigeminal nucleus. Being an aspect of untreated migraine, allodynia is more common in patients with chronic migraine and migraine with aura, often associated with motor and sensory symptoms sometimes present during the attacks. The presence of allodynia in the course of migraine attack greatly increases the disability of the patient and its recognition, as well as from a therapeutic point of view, it is essential in the management of migraine patients.
Topics: Animals; Humans; Hyperalgesia; Migraine Disorders; Trigeminal Nuclei
PubMed: 22644161
DOI: 10.1007/s10072-012-1034-9 -
Pain May 2019Mechanical allodynia is pain caused by normally innocuous mechanical stimuli and is a cardinal and intractable symptom of neuropathic pain. Roles of low-threshold... (Review)
Review
Mechanical allodynia is pain caused by normally innocuous mechanical stimuli and is a cardinal and intractable symptom of neuropathic pain. Roles of low-threshold mechanoreceptors (LTMRs), including Aβ fibers, in mechanical allodynia have previously been proposed, but the necessity and sufficiency of LTMRs in allodynia have not been fully determined. Recent technological advances have made it possible to achieve subpopulation-specific ablation, silencing or stimulation, and to dissect and elucidate complex neuronal circuitry. Recent studies using an optogenetic approach have shown that activation of LTMRs, including Aβ fibers that genetically express channelrhodopsin-2, by illuminating blue light to the skin elicit morphine-resistant withdrawal behaviors after nerve damage. Whole-cell recording has revealed that optical Aβ stimulation after nerve injury causes excitation of lamina I dorsal horn neurons, which are normally silent by this stimulation. Moreover, Aβ stimulation after nerve injury results in activation of central amygdaloid neurons and produces aversive behaviors. In summary, these findings indicate that optogenetics is a powerful approach for investigating LTMR-derived pain (resembling mechanical allodynia) with sensory and emotional features after nerve injury and for discovering novel and effective drugs to treat neuropathic pain.
Topics: Animals; Humans; Hyperalgesia; Neuralgia; Optogenetics; Pain Measurement; Pain Threshold
PubMed: 31008850
DOI: 10.1097/j.pain.0000000000001506 -
Journal of Obstetrics and Gynaecology... Mar 2016Cutaneous allodynia (pain from a non-painful stimulus) is a sign that can be observed among women with chronic pelvic pain. Dysmenorrhea is recognized as a common cause...
OBJECTIVE
Cutaneous allodynia (pain from a non-painful stimulus) is a sign that can be observed among women with chronic pelvic pain. Dysmenorrhea is recognized as a common cause of chronic pelvic pain in women. This study was conducted to explore the frequency of allodynia and the relationship between allodynia and severe dysmenorrhea.
METHODS
We enrolled women in this study if they had experienced chronic pelvic pain for more than six months. Women provided information regarding their chronic pelvic pain and menstrual function, specifically the severity of their menstrual pain. In addition to a gynaecological assessment, women were tested for allodynia and pain pressure thresholds.
RESULTS
Abdominal allodynia was present in 62.1% of 181 women who participated. Women with allodynia had a significantly greater rate of severe dysmenorrhea and significantly greater duration of severe dysmenorrhea. Pain pressure thresholds were demonstrated to decrease significantly in relation to increasing duration of severe dysmenorrhea.
CONCLUSION
There is a greater frequency of chronic pain among women with a history of severe dysmenorrhea. Women who experienced prolonged severe dysmenorrhea were shown to have a progressive increase in pain sensitivity (reflected in reduced pain pressure thresholds). These findings support efforts to manage dysmenorrhea early in a woman's life with approaches to suppress menstrual function.
Topics: Adult; Chronic Pain; Cohort Studies; Dysmenorrhea; Female; Humans; Hyperalgesia; Middle Aged; Pain Threshold; Pelvic Pain
PubMed: 27106198
DOI: 10.1016/j.jogc.2016.02.001 -
Current Pain and Headache Reports Apr 2010Cutaneous allodynia (CA), the perception of pain when a non-noxious stimulus is applied to normal skin, has been described in various pain syndromes. The pathophysiology... (Review)
Review
Cutaneous allodynia (CA), the perception of pain when a non-noxious stimulus is applied to normal skin, has been described in various pain syndromes. The pathophysiology of CA in headache is thought to be related to central sensitization of brainstem, and possibly thalamic, neurons. The recognition of CA in cluster headache (CH) is recent, and available data are scant. Some studies suggest the occurrence of CA in a significant proportion of CH patients. However, one study that examined sensory thresholds in CH failed to confirm this. CA in CH is characterized by rapid onset and termination, suggesting different mechanisms compared with CA in migraine. CA in CH is common in trigeminal areas but may spread to cervical dermatomes and beyond. The relations between the type of CH (episodic vs chronic) and CA are unknown. Further studies are needed to determine the mechanism of CA in CH, and its clinical implications.
Topics: Cluster Headache; Humans; Hyperalgesia; Skin
PubMed: 20425203
DOI: 10.1007/s11916-010-0097-7 -
Physiological Reviews Apr 2009Hyperalgesia and allodynia are frequent symptoms of disease and may be useful adaptations to protect vulnerable tissues. Both may, however, also emerge as diseases in... (Review)
Review
Hyperalgesia and allodynia are frequent symptoms of disease and may be useful adaptations to protect vulnerable tissues. Both may, however, also emerge as diseases in their own right. Considerable progress has been made in developing clinically relevant animal models for identifying the most significant underlying mechanisms. This review deals with experimental models that are currently used to measure (sect. II) or to induce (sect. III) hyperalgesia and allodynia in animals. Induction and expression of hyperalgesia and allodynia are context sensitive. This is discussed in section IV. Neuronal and nonneuronal cell populations have been identified that are indispensable for the induction and/or the expression of hyperalgesia and allodynia as summarized in section V. This review focuses on highly topical spinal mechanisms of hyperalgesia and allodynia including intrinsic and synaptic plasticity, the modulation of inhibitory control (sect. VI), and neuroimmune interactions (sect. VII). The scientific use of language improves also in the field of pain research. Refined definitions of some technical terms including the new definitions of hyperalgesia and allodynia by the International Association for the Study of Pain are illustrated and annotated in section I.
Topics: Animals; Disease Models, Animal; Female; Hyperalgesia; Male; Neuronal Plasticity; Nociceptors; Rats; Spinal Nerves; Touch
PubMed: 19342617
DOI: 10.1152/physrev.00025.2008 -
Journal of Opioid Management 2017Opioid analgesics are one of the most often prescribed medication classes, and their use has increased dramatically, with the number of prescriptions doubling between... (Review)
Review
Opioid analgesics are one of the most often prescribed medication classes, and their use has increased dramatically, with the number of prescriptions doubling between 1998 and 2010. Moreover, long-term use of opioids is becoming more prevalent. The complications arising from opioid use have been clearly documented; however, a relatively unknown complication potentially linked to opioid use is allodynia. This article outlines how research on opioid-induced hyperalgesia has led to the discovery of allodynia. Next, this article provides a detailed review of the current literature on allodynia, which includes animal studies, case reports, case series, and randomized controlled trials. Finally, the authors provide some potential clinical implications and applications for clinicians in regards to prescribing practices of opioids in the presence of allodynia.
Topics: Analgesics, Opioid; Animals; Evidence-Based Medicine; Humans; Hyperalgesia; Pain; Randomized Controlled Trials as Topic
PubMed: 28829524
DOI: 10.5055/jom.2017.0373 -
Neuroscience Letters Aug 2022Mechanical allodynia has been studied in chronic naltrexone-treated people (N.T.P.) and rats (N.T.R.). After persistent naltrexone administration, patients acquired...
Mechanical allodynia has been studied in chronic naltrexone-treated people (N.T.P.) and rats (N.T.R.). After persistent naltrexone administration, patients acquired static and dynamic mechanical allodynia, as measured by von Frey filament (vFf) and brush stimulations. Pregabalin and levodopa administrations in N.T.P. significantly reduced allodynic behaviour, albeit these molecules did not completely stop it. As evidenced by the deployment of the vFf, subchronic treatment with Naltrexone delivered peripherally or intrathecally induced allodynic behaviour in rats. Increased expressions of two pain markers, pERK1/2 and PKCγ, in the spinal dorsal horn laminae were associated with naltrexone-induced allodynic behaviour. After vFf stimulation, pERK1/2 expression was substantially higher (p < 0.001) in superficial spinal dorsal horn laminae than in non-stimulated or naive non-stimulated rats. In addition, when compared to control rats, N.T.R. showed a substantial (p < 0.001) increase in PKCγ expression. PKCγ expression was found to be strong in lamina IIi and laminae III-IV. A cellular mechanism is proposed for the naltrexone effect. In both people and rats, Naltrexone induces static mechanical allodynia, according to this study.
Topics: Animals; Humans; Hyperalgesia; Naltrexone; Pain; Rats; Rats, Sprague-Dawley; Spinal Cord Dorsal Horn
PubMed: 35901909
DOI: 10.1016/j.neulet.2022.136816 -
Clinical Neurology and Neurosurgery Sep 2022Cutaneous allodynia (CA) is a common symptom in migraine. Its incidence is more frequent in the chronic migraine (CM). CA usually occurs during pain attacks. However, it...
OBJECTIVE
Cutaneous allodynia (CA) is a common symptom in migraine. Its incidence is more frequent in the chronic migraine (CM). CA usually occurs during pain attacks. However, it can also be interictal and its frequency and severity seem to be correlated with the duration of the disease. Several quantitative sensory testing (QST) studies have revealed variable results about mechanical and thermal allodynia accompanying migraine. This study aimed to investigate the effects of CA and onabotulinumtoxinA (BoNT-A) injection on the thermal thresholds measured by QST in patients with CM. The effects of BoNT-A on headaches, CA, and other accompanying symptoms of migraine were also evaluated.
METHODS
Single BoNT-A injections were performed in 22 female cases (mean age: 38.1 ± 7.2 years) with CM. Patients were evaluated at 1-7 days before, 28-35, and 84-91 days after the injection. The 22 healthy women in the control group (mean age: 36.6 ± 7.6 years) were examined once. Headache and its characteristics, medication intake, allodynia, presence of anxiety, and depression symptoms were evaluated through relevant scales. The heat (HDT) and cold (CDT) detection thresholds on the forehead and hand were measured bilaterally with QST. The presence of brush allodynia for patients was examined by applying a 4 × 4 gauze pad over the same areas.
RESULTS
The patients in the CM group had migraine for an average of 22.5 ± 6.1 years and CM for 6.1 ± 3.2 years. The average number of painful days per month was 22.1 ± 4.0 days. All the patients had migraine attacks with CA (mean 5.6/month). The average allodynia symptom checklist (ASC-12) score was 7.8 ± 6.2. Thermal thresholds measured in the patients with CM were similar to those of the controls. Thermal thresholds did not show significant differences between the symptomatic and the asymptomatic sides at the last migraine attack. There was also no correlation between the allodynia revealed by the physical examination and the thermal thresholds detected by QST. The ASC-12 score decreased significantly with BoNT-A injection (p = 0.030), but no significant change was observed in thermal thresholds after this treatment.
CONCLUSION
There was no significant correlation between CA and thermal thresholds. BoNT-A was successful in relieving headache and other associated symptoms, including CA, but had no significant effect on QST parameters.
Topics: Adult; Botulinum Toxins, Type A; Female; Headache; Humans; Hyperalgesia; Middle Aged; Migraine Disorders; Pain
PubMed: 35792471
DOI: 10.1016/j.clineuro.2022.107357 -
Journal of Neuroinflammation Jan 2020Nerve injury-induced chronic pain has been an urgent problem for both public health and clinical practice. While transition to chronic pain is not an inevitable... (Review)
Review
Nerve injury-induced chronic pain has been an urgent problem for both public health and clinical practice. While transition to chronic pain is not an inevitable consequence of nerve injuries, the susceptibility/resilience factors and mechanisms for chronic neuropathic pain after nerve injuries still remain unknown. Current preclinical and clinical studies, with certain notable limitations, have shown that major histocompatibility complex class II-restricted T helper (Th) cells is an important trigger for nerve injury-induced chronic tactile allodynia, one of the most prevalent and intractable clinical symptoms of neuropathic pain. Moreover, the precise pathogenic neuroimmune interfaces for Th cells remain controversial, not to mention the detailed pathogenic mechanisms. In this review, depending on the biology of Th cells in a neuroimmunological perspective, we summarize what is currently known about Th cells as a trigger for chronic tactile allodynia after nerve injuries, with a focus on identifying what inconsistencies are evident. Then, we discuss how an interdisciplinary perspective would improve the understanding of Th cells as a trigger for chronic tactile allodynia after nerve injuries. Finally, we hope that the expected new findings in the near future would translate into new therapeutic strategies via targeting Th cells in the context of precision medicine to either prevent or reverse chronic neuropathic tactile allodynia.
Topics: Animals; Chronic Disease; Humans; Hyperalgesia; Major Histocompatibility Complex; T-Lymphocytes, Helper-Inducer
PubMed: 31900220
DOI: 10.1186/s12974-019-1684-0