Pain
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Randomized Controlled Trial Multicenter Study Comparative Study
Efficacy and safety of tanezumab in the treatment of chronic low back pain.
Increased nerve growth factor levels are associated with chronic pain conditions, including chronic low back pain (LBP). This study examined safety and analgesic efficacy of tanezumab, a humanized anti-nerve growth factor antibody, in adults with chronic LBP. Patients received intravenous tanezumab 200 μg/kg plus oral placebo (n=88), intravenous placebo plus oral naproxen 500 mg twice a day (n=88), or intravenous placebo plus oral placebo (n=41). ⋯ Nine patients (4 of whom were tanezumab-treated) discontinued due to AEs. In conclusion, tanezumab resulted in analgesic efficacy that was clinically and statistically superior to placebo and naproxen in patients with chronic LBP. Tanezumab clinical development is on regulatory hold due to AEs in osteoarthritis patients.
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The evidence for an association between leisure-time physical activity and prevalence of pain is insufficient. This study investigated associations between frequency, duration, and intensity of recreational exercise and chronic pain in a cross-sectional survey of the adult population of a Norwegian county (the Nord-Trøndelag Health Study; HUNT 3). Of the 94,194 invited to participate, complete data were obtained from 46,533 participants. ⋯ Dependent on the load of exercise, the prevalence of chronic pain was 21-38% lower among older women who exercised, relative to those not exercising. Similar, but somewhat weaker, associations were seen for older men. This study shows consistent and linear associations between frequency, duration, and intensity of recreational exercise and chronic pain for the older population, and associations without an apparent linear shape for the working-age population.
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Peripheral serotonin (5HT) has been implicated in migraine and temporomandibular pain disorders in humans and animal models and yet the mechanism(s) by which 5HT evokes pain remains unclear. Trigeminal pain can be triggered by activation of the transient receptor potential V1 channel (TRPV1), expressed by a subset of nociceptive trigeminal ganglia (TG) neurons and gated by capsaicin, noxious heat, and other noxious stimuli. As 5HT is released in the periphery during inflammation and evokes thermal hyperalgesia, and TRPV1 is essential for thermal hyperalgesia, we hypothesized that 5HT increases the activity of capsaicin-sensitive trigeminal neurons and that this increase can be attenuated by pharmacologically targeting peripheral 5HT receptors. ⋯ In addition, using in situ hybridization and immunohistochemistry, we detected the colocalization of 5HT(1B), 5HT(1D), 5HT(2A), and 5HT(3A), but not 5HT(2C) mRNA with TRPV1 in TG cells. 5HT pretreatment evoked a significant increase in calcium accumulation in capsaicin-sensitive trigeminal neurons and enhanced capsaicin-evoked CGRP release, but had no significant effect when given alone. Sumatriptan, ketanserin, and granisetron treatment attenuated calcium accumulation and 5HT enhancement of capsaicin-evoked CGRP release. Together these results indicate that 5HT increases the activity of capsaicin-sensitive peripheral nociceptors, which can be attenuated by pharmacologically targeting peripheral 5HT receptors, thereby providing a mechanistic basis for peripheral craniofacial pain therapy.
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Venoms peptides have produced exceptional sources for drug development to treat pain. In this study we examined the antinociceptive and side effects of Tx3-3, a peptide toxin isolated from Phoneutria nigriventer venom, which inhibits high-voltage-dependent calcium channels (VDCC), preferentially P/Q and R-type VDCC. We tested the effects of Tx3-3 in animal models of nociceptive (tail-flick test), neuropathic (partial sciatic nerve ligation and streptozotocin-induced diabetic neuropathy), and inflammatory (intraplantar complete Freund's adjuvant) pain. ⋯ On the other hand, i.t. injection of Tx3-3 did not alter inflammatory pain. Taken together, our data show that Tx3-3 shows prevalent antinociceptive effects in the neuropathic pain models and does not cause adverse motor effects at antinociceptive efficacious doses, suggesting that this peptide toxin holds promise as a novel therapeutic agent for the control of neuropathic pain. The Brazilian armed spider Tx3-3, a new P/Q and R-type calcium channel blocker, effectively alleviates allodynia in animal neuropathic pain models.
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Controlled Clinical Trial
Structural abnormalities of the trigeminal root revealed by diffusion tensor imaging in patients with trigeminal neuralgia caused by neurovascular compression: a prospective, double-blind, controlled study.
Because diffusion tensor imaging (DTI) is able to assess tissue integrity, we used diffusion to detect abnormalities in trigeminal nerves (TGN) in patients with trigeminal neuralgia (TN) caused by neurovascular compression (NVC). We also studied anatomical TGN parameters (cross-sectional area [CSA] and volume [V]). Using DTI sequencing in a 3-T magnetic resonance imaging (MRI) scanner, we measured the fraction of anisotropy (FA) and the apparent diffusion coefficient (ADC) of TGN in 10 patients selected as candidates to have microvascular decompression (MVD) for TN, and 6 normal control subjects. ⋯ The Spearman correlation coefficient showed a strong negative correlation between increase in ADC and loss of V (r=-0.7173) and loss of CSA (r=-0.7416) in affected nerves. DTI revealed alteration in the FA and ADC values of the affected TGN. These alterations were correlated with atrophic changes in patients with TN caused by NVC.