Articles: neuralgia.
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Objectives. Overweight negatively affects musculoskeletal health; hence obesity is considered a risk factor for osteoarthritis and chronic low back pain. This was conducted to determine if obesity affects neuropathic pain, usually considered unrelated to the weight-load on the musculoskeletal system. ⋯ Neuropathic pain that did not arise from musculoskeletal damage was higher in the high-BMI patients. Paroxysmal pain was more severe, suggesting that neural damage might be aggravated by obesity-associated inflammation. These findings should have needed to be confirmed in future studies.
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As the biological alarm of impending or actual tissue damage, pain is essential for our survival. However, when it is initiated and/or sustained by dysfunctional elements in the nociceptive system, it is itself a disease known as neuropathic pain. While the critical nociceptive system provides a number of protective functions, it is unique in its central role of monitoring, preserving and restoring the optical tear film in the face of evaporative attrition without which our vision would be non-functional. ⋯ The clinical consequences of corneal damage to these nociceptive pathways are determined by the type and location of its pathological elements and can range from the spectrum known as dry eye disease to the centalised oculofacial neuropathic pain syndrome characterised by a striking disparity between the high intensity of symptoms and paucity of external signs. These changes parallel those observed in somatic neuropathic pain. When seen through the neuroscience lens, diseases responsible for inadequately explained chronic eye pain (including those described as dry eye) can take on new meanings that may clarify long-standing enigmas and point to new approaches for developing preventive, symptomatic and disease-modifying interventions for these currently refractory disorders.
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Randomized Controlled Trial
Exposure-response modeling of average daily pain score, and dizziness and somnolence, for mirogabalin (DS-5565) in patients with diabetic peripheral neuropathic pain.
Mirogabalin (DS-5565) is an α2δ-1 ligand being developed for pain associated with diabetic peripheral neuropathy, fibromyalgia, and postherpetic neuralgia. Nonlinear mixed-effects analyses were performed on average daily pain and on the incidence of the adverse events dizziness and somnolence. These models were used to predict the dose of mirogabalin equivalent to pregabalin and the probability of meaningful reduction in pain compared with placebo and pregabalin. ⋯ The incidence rate of dizziness and somnolence decreased over time. Twice-daily dosing of mirogabalin was predicted to yield a lower incidence rate of dizziness than once-daily dosing; thus, titration of dosages should reduce adverse event rates. These model results were used to influence phase 3 dosing selection.
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Neuropathic characteristics are highly involved in the development of chronic pain both physically and psychologically. However, little is known about the relationship between neuropathic characteristics and brain morphological alteration. ⋯ Our findings suggest that neuropathic characteristics strongly affect the brain regions related to modulation of pain in patients with chronic pain and, therefore, contribute to the severity of chronic pain.
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The use of rodents in preclinical studies has contributed greatly to our understanding of the pathophysiology of chronic neuropathic pain. These animal models are limited because of their poor clinical translation. We developed a pig model for chronic pain caused by surgically induced peripheral neuritis trauma (PNT). Seventy-five percent of the animals exhibited mechanical and tactile allodynia, which are indicative of painful neuropathy, by day 28 after surgery. Importantly, the PNT-injured pigs retained their ability to walk or to stand on their injured leg. Messenger RNA analysis of acute inflammatory cytokines calcitonin gene-related peptide and brain-derived neurotrophic factor at the site of injury suggests transient inflammation followed by a persistent high level of neurologic markers. Gabapentin and morphine effectively inhibited hypersensitivity to von Frey filaments and to feather stimuli, and reversed spontaneous pain-related behavior in a dose-related manner. No analgesic effect was detected in PNT-injured pigs after treatment with aprepitant, similar to observations in humans and contrary to observations in rodents. In conclusion, PNT-induced trauma in pigs may comprise a valid preclinical model for the study of the chronification of peripheral nerve injury and for the study of new pain therapies. ⋯ This article presents the characterization of a new peripheral neuritis trauma (PNT) model in pigs. The pig PNT model could help close the translational gap between preclinical and clinical responses and may contribute to improved efficacy or safety of candidate drugs.