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Provoked vestibulodynia (PVD) is a chronic vulvo-vaginal pain condition affecting 8% of premenopausal women. Cognitive-behavioral therapy (CBT) is effective in managing pain and associated sexual and psychological symptoms, and a recent study found group mindfulness-based cognitive therapy (MBCT) to be equivalent. Our goal was to examine the long-term outcomes of these treatments and to explore mediators of change.
Clinically relevant chronic pain is often associated with functional impairment and behavioral depression as an "affective/motivational" sign of pain; however preclinical animal models of inflammatory and neuropathic pain often produce weak evidence of impaired function. We hypothesized that hindpaw mechanical stimulation produced by a requirement to rear on a textured "NOX" plate would punish operant responding in rats treated with intraplantar complete Freund's adjuvant (CFA, a model of inflammatory pain) or the chemotherapeutic paclitaxel (PTX, a model of neuropathic pain) and produce sustained pain-related depression of operant behavior. Male Sprague-Dawley rats were trained under a progressive-ratio (PR) schedule of food-maintained operant responding, then treated with CFA (100 µL in left hindpaw), PTX (2.0 mg/kg IP on alternate days for four total injections; 6.6 mg/kg IV on alternate days for three total injections), or saline vehicle. PR break points and mechanical thresholds for paw withdrawal from von Frey filaments were then tracked for 28 days. Subsequently, rats were tested with the opioid receptor antagonist naltrexone to assess latent sensitization and with the kappa opioid receptor (KOR) agonist U69593 to assess KOR function. CFA produced significant mechanical hypersensitivity for 3 weeks but decreased PR breakpoints for only 1 day. Both IP and IV PTX produced mechanical hypersensitivity for at least three weeks; however, only IV PTX decreased PR breakpoints, and this decrease was not alleviated by morphine. After recovery, naltrexone reinstated mechanical hypersensitivity in CFA- but not PTX-treated rats, and it did not reinstate depression of breakpoints in any group. U69593 dose-dependently decreased PR breakpoints in all groups with no difference between control vs. CFA/PTX groups. These results suggest that rearing on a textured NOX plate was not sufficient to punish operant responding in CFA- and PTX-treated rats despite the presence of sustained mechanical hypersensitivity. The rapid recovery of operant responding could not be attributed to latent sensitization, KOR downregulation, or behavioral tolerance. These results extend the range of conditions under which putative chronic pain manipulations produce weak evidence for depression of operant responding as a sign of the "affective/motivational" component of pain in rats.
Evaluate changes from baseline in health-related quality of life (QoL) in Japanese patients with episodic migraine receiving preventive treatment with galcanezumab (GMB).
Coping strategies and their efficacy vary greatly in patients suffering from fibromyalgia syndrome (FMS).
To compare the prevalence of psychiatric comorbidity between patients with complex regional pain syndrome (CRPS) of the hand and non-CRPS patients and to assess the association between biopsychosocial (BPS) complexity profiles and psychiatric comorbidity in a comparative study.
It is known that perivascular application of CGRP induces cerebral vasodilatation. However, it is unclear whether intravenous alfa CGRP (αCGRP) induces changes in cerebral and systemic hemodynamics. Therefore, we studied the influence of an αCGRP intravenous infusion at a rate of 1.5 mcg/min in 20 min on mean arterial velocity in the middle cerebral artery (vm MCA) and in the posterior cerebral artery (vm PCA) in twenty healthy subjects using transcranial Doppler (TCD). We found out that αCGRP decreased vm MCA ( < 0.001), vm PCA ( < 0.001), mean arterial pressure (MAP) ( < 0.001) and end-tidal CO (Et-CO) ( = 0.030). The heart rate (HR) increased during αCGRP infusion ( < 0.001). In addition, we found a positive relationship between Et-CO and vm MCA ( = 0.001) as well as vm PCA ( = 0.043). In our view, αCGRP induces changes in cerebral and systemic circulation in healthy volunteers. It might cause vasodilatation of MCA and PCA and a compensatory decrease of Et-CO to αCGRP related hemodynamic changes.
The development of highly efficacious alternatives to mu-opioid analgesics represents an urgent unmet medical and public health need. In the presence of inflammation both delta- and kappa-opioid agonists, acting on peripheral sensory neurons, mediate analgesia. The dual-acting, peripherally restricted kappa/delta-opioid agonist, CAV1001, was tested in four rodent pain models.
The earliest descriptions of botulism were in the early 19th century, and was reported by the German physician Justinus Kerner. The term "botulism" was derived from the Latin word botulus, indicating its original association with sausages. It took another 150 years or so to come into clinical use. The first clinical application was strabismus, and was developed by the American ophthalmologist Alan B. Scott, whose effort led to the pharmaceutical product known as onabotulinumtoxinA today. The therapeutic benefit in migraine was an incidental finding in a report by the American plastic surgeon William J. Binder, which inspired a series of clinical studies in headache disorders. The doses and injection techniques in the earlier reports were variable, so were the results. It was until the Phase III REsearch Evaluating Migraine Prophylaxis Therapy (PREEMPT) 1 and 2 studies when its efficacy and safety, as well as the indication, i.e., chronic migraine (CM), were ascertained. Even though there were criticisms regarding the heterogeneities in the results between the PREEMPT 1 and 2 studies, the data on efficacy endpoints and safety were generally consistent, which were subsequently confirmed by the open-label extension of the PREEMPT 1 and 2 studies, and three open-label studies, namely the Chronic Migraine OnabotulinuMtoxinA Prolonged Efficacy open Label (COMPEL), the REal-life use of botulinum toxin for the symptomatic treatment of adults with chronic migraine, measuring healthcare resource utilization, and Patient-reported OutcomeS observed in practice (REPOSE) studies, and the CM Post-Authorization Safety Study (CM PASS) studies. On the other hand, the results were challenged by the Chronification and Reversibility of Migraine (CHARM) study, which involved CM patients with medication overuse. It was concluded that the clinical improvement was attributed to early withdrawal of the overused acute medications, rather than onabotulinumtoxinA injections. However, fundamental differences in the patient profile and methodology between the CHARM and PREEMPT studies existed, and cautious should be exercised when interpreting and comparing the results. According to the practical guidelines and reimbursement regulations in many countries, its use is limited to CM patients, and is reserved for those who fail at least 2-3 preventive medications, due to either lack of efficacy or intolerability. Cessation of treatment is recommended in patients who do not respond to 2-3 injection cycles, or in patients whose headache frequency has dropped to <10-15 days a month. Even in the era of calcitonin-gene-related peptide monoclonal antibodies, onabotulinumtoxinA injection remains a treatment option of reasonable cost-effectiveness in carefully selected patients.
Chronic pain, particularly that following nerve injury, can occur in the absence of external stimuli. Although the ongoing pain is sometimes continuous, in many individuals the intensity of their pain fluctuates. Experimental animal studies have shown that the brainstem contains circuits that modulate nociceptive information at the primary afferent synapse and these circuits are involved in maintaining ongoing continuous neuropathic pain. However, it remains unknown if these circuits are involved in regulating fluctuations of ongoing neuropathic pain in humans.