Pain
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Despite the increasing interest in TRPA1 channel as a pain target, its role in cold sensation and body temperature regulation is not clear; the efficacy and particularly side effects resulting from channel blockade remain poorly understood. Here we use a potent, selective, and bioavailable antagonist to address these issues. A-967079 potently blocks human (IC(50): 51 nmol/L, electrophysiology, 67 nmol/L, Ca(2+) assay) and rat TRPA1 (IC(50): 101 nmol/L, electrophysiology, 289 nmol/L, Ca(2+) assay). ⋯ Unlike TRPV1 antagonists, A-967079 does not alter body temperature. It also does not produce locomotor or cardiovascular side effects. Collectively, these data provide novel insights into TRPA1 function and suggest that the selective TRPA1 blockade may present a viable strategy for alleviating pain without untoward side effects.
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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.