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Conditioned Pain Modulation (CPM) and Manipulation Induced Analgesia (MIA) may activate similar neurophysiological mechanisms to mediate their analgesic effects. This study assessed the association between CPM and MIA responses in people with lateral epicondylalgia (LE).
Learn More >Inflammatory pain is associated with peripheral and central sensitization, but the underlying synaptic plasticity at the spinal cord level is poorly understood. Transient receptor potential (TRP) channels expressed at peripheral nerve endings, including TRPA1 and TRPV1, can detect nociceptive stimuli. In this study, we determined the contribution of presynaptic TRPA1 and TRPV1 at the spinal cord level to regulating nociceptive drive in chronic inflammatory pain induced by treatment with complete Freund's adjuvant (CFA) in rats. CFA treatment caused a large increase in the frequency of spontaneous excitatory postsynaptic currents (EPSCs) in lamina I, but not lamina II outer zone, dorsal horn neurons. However, blocking NMDA receptors had no effect on spontaneous EPSCs in lamina I neurons of CFA-treated rats. Application of a specific TRPA1 antagonist, AM-0902, or of a specific TRPV1 antagonist, 5'-iodoresiniferatoxin, significantly attenuated the elevated frequency of spontaneous EPSCs and miniature EPSCs, the amplitude of monosynaptic EPSCs evoked from the dorsal root in lamina I neurons of CFA-treated rats. AM-0902 and 5'-iodoresiniferatoxin had no effect on evoked or miniature EPSCs in lamina I neurons of vehicle-treated rats. In addition, intrathecal injection of AM-0902 or 5'-iodoresiniferatoxin significantly reduced pain hypersensitivity in CFA-treated rats but had no effect on acute nociception in vehicle-treated rats. These findings suggest that chronic inflammatory pain is associated with NMDA receptor-independent potentiation in glutamatergic drive to spinal lamina I neurons. Endogenous presynaptic TRPA1 and TRPV1 activity at the spinal level contributes to increased nociceptive input from primary sensory nerves to dorsal horn neurons in inflammatory pain. This article is protected by copyright. All rights reserved.
Learn More >Pain-related cues are evolutionarily primed to capture attention, although evidence of attentional biases towards pain-related information is mixed in healthy individuals. The present study explores whether healthy individuals show significantly different eye-movement behaviours when viewing real-world pain-related scenes compared to neutral scenes. The effect of manipulating via written information the threat value of the pain-related scenes on eye-movement behaviours was also assessed.
Learn More >Vulvodynia is a remarkably prevalent chronic pain condition of unknown etiology. An increase in numbers of vulvar mast cells often accompanies a clinical diagnosis of vulvodynia and a history of allergies amplifies the risk of developing this condition. We previously showed that repeated exposures to oxazolone dissolved in ethanol on the labiar skin of mice led to persistent genital sensitivity to pressure and a sustained increase in labiar mast cells. Here we sensitized female mice to the hapten dinitrofluorobenzene (DNFB) dissolved in saline on their flanks, and subsequently challenged them with the same hapten or saline vehicle alone for ten consecutive days either on labiar skin or in the vaginal canal. We evaluated tactile ano-genital sensitivity, and tissue inflammation at serial timepoints. DNFB-challenged mice developed significant, persistent tactile sensitivity. Allergic sites showed mast cell accumulation, infiltration of resident memory CD8CD103 T cells, early, localized increases in eosinophils and neutrophils, and sustained elevation of serum Immunoglobulin E (IgE). Therapeutic intra-vaginal administration of Δ-tetrahydrocannabinol (THC) reduced mast cell accumulation and tactile sensitivity. Mast cell-targeted therapeutic strategies may therefore provide new ways to manage and treat vulvar pain potentially instigated by repeated allergenic exposures.
Learn More >Quantitative sensory testing (QST) is a formal variant of a time-honoured clinical examination technique in neurology, the sensory examination. Prototypical QST profiles have been found in human surrogate models of peripheral sensitization, central sensitization, and deafferentation. Probabilistic sorting of individual patients to any combination of these profiles has been developed, and there is emerging evidence for the predictive value of such sensory profiles for treatment efficacy. This way, QST aids in diagnostics of individual patients and may help guide their care in the future. Deficits in "dynamic" QST have been proposed as predictors of chronic pain (impaired descending inhibition and delayed recovery from central sensitization). Several psychological factors had previously been found to be predictors of pain chronicity (catastrophizing, self-efficacy, and neuroticism). The relative importance of psychological vs sensory testing predictors has not been evaluated. It is likely that both will have differential roles in clinical practice.
Learn More >Migraine is a common, severe disease, affecting the brain and blood vessels, causing much pain, time missed from work and family, and severe disability. It affects approximately 12% of most Western populations studied and affects women three times more than men. Cluster headache is a much less common dysfunction of the hypothalamus, involving the sphenopalatine ganglion and other areas; it causes more frequent, shorter, and even more intense pain than migraine. The pain usually comes in cycles and is associated with ipsilateral autonomic features and associated with irritability and inability to stay still. It affects less than 0.1% of the population and is slightly more prevalent in men than women. Although we have some acute care and preventive medications for both types of headache, no treatment is optimal for each patient and some will not respond well or have significant adverse events to existing therapies.
Learn More >Reports in the literature have conflicting findings about an association between dry eye disease (DED) and migraine headaches.
Learn More >While evidence indicates that sigma-1 receptors (Sig-1Rs) play an important role in the induction of peripheral neuropathic pain, there is limited understanding of the role that the neurosteroidogenic enzymes, which produce Sig-1R endogenous ligands, play during the development of neuropathic pain. We examined whether sciatic nerve injury upregulates the neurosteroidogenic enzymes, cytochrome P450c17 and 3β-hydroxysteroid dehydrogenase (3β-HSD), which modulate the expression and/or activation of Sig-1Rs leading to the development of peripheral neuropathic pain. Chronic constriction injury (CCI) of the sciatic nerve induced a significant increase in the expression of P450c17, but not 3β-HSD, in the ipsilateral lumbar spinal cord dorsal horn at postoperative day 3. Intrathecal administration of the P450c17 inhibitor, ketoconazole during the induction phase of neuropathic pain (day 0 to day 3 post-surgery) significantly reduced the development of mechanical allodynia and thermal hyperalgesia in the ipsilateral hind paw. However, administration of the 3β-HSD inhibitor, trilostane had no effect on the development of neuropathic pain. Sciatic nerve injury increased astrocyte Sig-1R expression as well as dissociation of Sig-1Rs from BiP in the spinal cord. These increases were suppressed by administration of ketoconazole, but not by administration of trilostane. Co-administration of the Sig-1R agonist, PRE084 restored the development of mechanical allodynia originally suppressed by the ketoconazole administration. However, ketoconazole-induced inhibition of thermal hyperalgesia was not affected by co-administration of PRE084. Collectively these results demonstrate that early activation of P450c17 modulates the expression and activation of astrocyte Sig-1Rs, ultimately contributing to the development of mechanical allodynia induced by peripheral nerve injury.
Learn More >Medication overuse headache (MOH) is the most prevalent chronic headache disorder with a prevalence between 1-2% worldwide. The disease has been acknowledged for almost 30 years, yet experts still disagree on how best to treat MOH. By performing a search in PubMed on the terms "medication overuse headache", "analgesics abuse headache", "rebound headache", "drug induced headache", and "headache AND drug misuse" limited to human studies published in English between January 1 2004 and November 1 2017, we aimed to evaluate current literature concerning predictors of treatment outcome, inpatient and outpatient treatment programs, initial versus latent administration of prophylactic medications, and to review the effect of prophylactic medications. Selection criteria were prospective, comparative or controlled trials on treatment of MOH in persons of at least 18 years of age. Several studies evaluated risk factors to predict the outcome of MOH treatment, but many studies were underpowered. Psychiatric comorbidity, high dependence score and overuse of barbiturates, benzodiazepines and opioids predicted a poorer outcome of withdrawal therapy. Patients with these risk factors benefit from inpatient treatment, whereas patients without risk factors benefit equally from in and outpatient treatment. Some medications for migraine prophylactics have shown better effect on MOH compared with placebo, but not when combined with withdrawal. We conclude that detoxification programs are of great importance in MOH treatment. Latent administration of prophylactic medications reduces the number of patients needing prophylactic medication. Individualizing treatment according to the predictors of outcome may improve treatment outcome and thus reduce work-related and treatment-related costs. This article is protected by copyright. All rights reserved.
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