Pain
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Despite the impact of chronic pain on the quality of life in patients, including changes to affective state and daily life activities, rodent preclinical models rarely address this aspect of chronic pain. To better understand the behavioral consequences of the tissue and nerve injuries typically used to model neuropathic and inflammatory pain in mice, we measured home cage and affective state behaviors in animals with spared nerve injury, chronic constriction injury (CCI), or intraplantar complete Freund's adjuvant. Mechanical hypersensitivity is prominent in each of these conditions and persists for many weeks. ⋯ Animals with CCI were initially less active, but the difference between CCI and controls disappeared by 2 weeks after injury. Further, in all pain models, there was no change in any measure of affective state. We conclude that in these standard models of persistent pain, despite the development of prolonged hypersensitivity, the mice do not have significantly altered "quality of life." As alteration in daily life activities is the feature that is so disrupted in patients with chronic pain, our results suggest that the models used here do not fully reflect the human conditions and point to a need for development of a murine chronic pain model in which lifestyle changes are manifest.
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Neuropeptide Y (NPY) has an important but still insufficiently defined role in pain modulation. We therefore examined the ability of NPY to modulate experimentally induced neuropathic pain by injecting it directly into dorsal root ganglion (DRG) immediately following spinal nerve ligation (SNL) injury. We have found that this application exacerbates pain-related behavior induced by SNL in a modality-specific fashion. ⋯ Exacerbation of pain-related behavior following NPY injection was accompanied by astrocyte activation in ipsilateral dorsal horn and with satellite cells activation in the DRG proximal to injury. This activation was reduced following Y2 receptor antagonist application. These findings indicate an important link between pain-related behavior and neuroimmune activation by NPY through its Y2 receptor.
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Meta Analysis Comparative Study
Minimum efficacy criteria for comparisons between treatments using individual patient meta-analysis of acute pain trials: examples of etoricoxib, paracetamol, ibuprofen, and ibuprofen/paracetamol combinations after third molar extraction.
We defined response in acute pain trials according to percentage of maximum possible efficacy. Minimum efficacy criteria (MEC) of 0%, or at least 15%, 30%, 50%, and 70% pain relief were used to examine stability over time using total pain relief and summed pain intensity difference (SPID), sex differences, and sensitivity. We used individual patient data from placebo-controlled third molar extraction trials: 4 with single-dose oral etoricoxib 120 mg, and 2 with paracetamol, ibuprofen, and ibuprofen plus paracetamol combinations. ⋯ The highest degree of discrimination between treatments was with MEC50 and MEC70. Etoricoxib 120 mg (NNT for ≥50% maximum 6-hour pain relief 1.7) and ibuprofen 200/400 mg plus paracetamol 500/1000 mg (NNTs 1.5 and 1.6, respectively) produced the lowest (best) NNTs in the dental pain model. Timing of patient request for additional analgesia is an alternative analgesic efficacy outcome measure.
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Randomized Controlled Trial Multicenter Study Clinical Trial
Safety and efficacy of pregabalin in patients with central post-stroke pain.
Pregabalin has demonstrated efficacy in several forms of neuropathic pain, but its long-term efficacy in central post-stroke pain (CPSP) is unproven. We evaluated the efficacy and safety of pregabalin versus placebo in patients with CPSP. A 13-week, randomized, double-blind, multicenter, placebo-controlled, parallel group study of 150 to 600 mg/day pregabalin was conducted in patients aged ≥18 years with CPSP. ⋯ Treatment with pregabalin resulted in significant improvements, compared with placebo, on secondary endpoints including MOS-sleep, HADS-A anxiety, and clinician global impression of change (CGIC) P<0.05. Adverse events were more frequent with pregabalin than with placebo and caused discontinuation in 9 (8.2%) of pregabalin patients versus 4 (3.7%) of placebo patients. Although pain reductions at endpoint did not differ significantly between pregabalin and placebo, improvements in sleep, anxiety, and CGIC suggest some utility of pregabalin in the management of CPSP.
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Randomized Controlled Trial Clinical Trial
Sodium oxybate reduces pain, fatigue, and sleep disturbance and improves functionality in fibromyalgia: results from a 14-week, randomized, double-blind, placebo-controlled study.
This 14-week, phase 3, double-blind, randomized, controlled trial evaluated sodium oxybate (SXB) 4.5 and 6g per night versus placebo in patients with fibromyalgia (FM). SXB is the sodium salt of γ-hydroxybutyrate (GHB). GHB is an endogenous compound, synthesized from γ-aminobutyric acid (GABA) and found broadly in the central nervous system and body. ⋯ The proportion of patients who reported a global improvement of "much" or "very much" better on the Patient Global Impression of Change was significantly greater in both SXB groups versus placebo (P<0.001). Headache, nausea, dizziness, vomiting, diarrhea, anxiety, and sinusitis were the most commonly reported adverse events, with an incidence at least twice that of placebo. These results expand the evidence from previous clinical trials suggesting that SXB is effective and safe in FM.