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Our knowledge of the pathophysiology of migraine and the molecules implicated in the disorder have evolved over time. Among these, calcitonin gene-related peptide has shown a crucial role that led to the development of therapies specifically targeting the molecule. Four monoclonal antibodies targeting the calcitonin gene-related peptide pathway are currently available after the US FDA approval of eptinezumab for the indication of migraine prevention. This is the only one of the class to be administered intravenously. The pharmacology of eptinezumab and the four studies that led to the approval, two Phase II and two Phase III clinical trials, are reviewed in this paper. Eptinezumab has demonstrated efficacy, tolerability and safety in patients with episodic and chronic migraine. Studies including migraineurs who have failed previous preventives, and comparison with other options administered quarterly, as well as real-world experience data will all be welcome.
Learn More >The purpose of this study was to compare disability in people with HIV and peripheral neuropathy with those without neuropathy and explore how neuropathy and other relevant factors are associated with disability.
Learn More >Low back pain (LBP) is a leading cause of disability. However, the processes contributing to disability are not well understood. Therefore, this study 1) empirically derived LBP subgroups and 2) validated these subgroups using walking performance, pain, and disability measures. Seventy adults with LBP underwent testing for a priori determined sensory (temporal summation; conditioned pain modulation), psychological (positive coping; negative coping), and motor (trunk extensor muscle activation during forward bending and walking) measures. A hierarchical cluster analysis determined subgroups that were then validated using walking (walking speed; Timed Up and Go (TUG); Timed Up and Go-Cognitive (TUG-Cog); obstacle negotiation) and clinical (Brief Pain Inventory; Oswestry Disability Index; low back pressure pain threshold) measures. Two subgroups were derived: 1) a "Maladaptive" subgroup (n=21) characterized by low positive coping, high negative coping, low pain modulation, and atypical trunk extensor activation; and 2) an "Adaptive" subgroup (n=49) characterized by high positive coping, low negative coping, high pain modulation, and typical trunk extensor activation. There were subgroup differences on 7 out of 12 validation measures. The Maladaptive subgroup had reduced walking performance (slower self-selected walking speed, TUG completion, and obstacle approach and crossing speed) and worse clinical presentation (higher pain intensity, pain interference, and disability) (moderate to large effect sizes; p's<0.05). Findings support the construct validity of this multidimensional subgrouping approach. Longitudinal studies are needed to determine if the Maladaptive subgroup is predictive of poor outcomes, such as pain chronicity or persistent disability.
Learn More >Nerve injury-induced changes in gene expression in the dorsal root ganglion (DRG) contribute to neuropathic pain genesis. Eukaryotic initiation factor 4 gamma 2 (eIF4G2) is a general repressor of cap-dependent mRNA translation. Whether DRG eIF4G2 participates in nerve injury-induced alternations in gene expression and nociceptive hypersensitivity is unknown.
Learn More >Inadequate acute pain management can reduce the quality of life, cause unnecessary suffering and can often lead to the development of chronic pain. Using group-based trajectory modelling, we previously identified six distinct pain intensity trajectories for the first 14-day postemergency department (ED) discharge; two linear ones with moderate or severe pain during follow-up (~40% of the patients) and four cubic polynomial order trajectories with mild or no pain at the end of the 14 days (low final pain trajectories). We assessed if previously described acute pain intensity trajectories over 14 days after ED discharge are predictive of chronic pain 3 months later.
Learn More >Population based cross-sectional study OBJECTIVE.: The aim of this study was to gain a better understanding of changes in muscle morphology in patients with chronic idiopathic neck pain (CINP) and whiplash associated disorder (CWAD).
Learn More >Total knee replacement (TKR) normally provides improvements of physical function and reduces pain. However, approximately 20% of the patients report chronic postoperative knee pain. The aims of the present study were to assess the pain, physical function, and physiological characteristics 5 years after TKR surgery.
Learn More >School-based educational programs have shown positive changes in health-related behaviors among adolescents. The aim of this study was to analyze the changes in pain-related knowledge among adolescents and in the use of positive responses to their peers' pain behaviors after watching a brief educational video.
Learn More >Benzodiazepines bind to and act on α1-3 and α5-containing GABAA receptors. Previous studies suggest that different GABAA receptor α-subtypes mediate the various behavioral effects of benzodiazepines, which raises the possibility of combining benzodiazepines with subtype-selective GABAA receptor antagonists to improve the therapeutic profiles of benzodiazepines. This study examined the GABAA receptor subtype mediation of the tolerance to midazolam-induced antinociception in rats. Midazolam (3.2 mg/kg) significantly reduced the locomotion in rats which was prevented by the selective α1-preferring GABAA receptor antagonist β-carboline-3-carboxylate-t-butyl ester (βCCt) (3.2 mg/kg). Midazolam increased the paw withdrawal threshold as tested by the von Frey filament assay in the complete Freund's adjuvant-induced inflammatory pain model in rats, and this effect was not altered by βCCt or another α1-preferring GABAA receptor antagonist 3-propoxy-β-carboline hydrochloride (3PBC). Repeated treatment with midazolam in combination with vehicle, βCCt or 3PBC (twice daily) for 7 days led to a progressive increase of the ED50 values in the midazolam- and vehicle-treated rats, but not in other rats, suggesting the development of tolerance to midazolam but not to the combination of midazolam with α1-preferring GABAA receptor antagonists. These results suggest the essential role of the α1-subtype of GABAA receptors in mediating the development of tolerance to midazolam-induced antinociceptive effects and raise the possibility of increasing therapeutic profiles of benzodiazepines by selectively blocking specific α-subtypes of GABAA receptors.
Learn More >The primary aim of this study was to examine sex differences in acute antinociceptive and anti-inflammatory effects of nonsteroidal anti-inflammatory drugs (NSAIDs) in rats. Complete Freund's adjuvant (CFA) was administered to adult Sprague-Dawley rats to induce pain and inflammation in one hindpaw; 2.5 h later, vehicle or a single dose of the NSAIDs ibuprofen (1.0-32 mg/kg) or ketoprofen (0.1-10 mg/kg), or the COX-2-preferring inhibitor celecoxib (1.0-10 mg/kg) was injected i.p. Mechanical allodynia, heat hyperalgesia, biased weight-bearing, and hindpaw thickness were assessed 0.5-24 h after drug injection. Ibuprofen and ketoprofen were more potent or efficacious in females than males in reducing mechanical allodynia and increasing weight-bearing on the CFA-injected paw, and celecoxib was longer-acting in females than males on these endpoints. In contrast, ketoprofen and celecoxib were more potent or efficacious in males than females in reducing hindpaw edema. When administered 3 days rather than 2.5 h after CFA, ketoprofen (3.2-32 mg/kg) was minimally effective in attenuating mechanical allodynia and heat hyperalgesia, and did not restore weight-bearing or significantly decrease hindpaw edema, with no sex differences in any effect. Neither celecoxib nor ketoprofen effects were significantly attenuated by cannabinoid receptor 1 or 2 (CB1 or CB2) antagonists in either sex. These results suggest that common NSAIDs administered shortly after induction of inflammation are more effective in females than males in regard to their antinociceptive effects, whereas their anti-inflammatory effects tend to favor males; effect sizes indicate that sex differences in NSAID effect may be functionally important in some cases.
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