Pain
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Histone deacetylase inhibitors (HDACIs) interfere with the epigenetic process of histone acetylation and are known to have analgesic properties in models of chronic inflammatory pain. The aim of this study was to determine whether these compounds could also affect neuropathic pain. Different class I HDACIs were delivered intrathecally into rat spinal cord in models of traumatic nerve injury and antiretroviral drug-induced peripheral neuropathy (stavudine, d4T). ⋯ The drugs globally increased histone acetylation in the spinal cord, but appeared to have no measurable effects in relevant dorsal root ganglia in this treatment paradigm, suggesting that any potential mechanism should be sought in the central nervous system. Microarray analysis of dorsal cord RNA revealed the signature of the specific compound used (MS-275) and suggested that its main effect was mediated through HDAC1. Taken together, these data support a role for histone acetylation in the emergence of neuropathic pain.
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Review Meta Analysis
Relationship between quantitative sensory testing and pain or disability in people with spinal pain-A systematic review and meta-analysis.
Sensitization of the nervous system can present as pain hypersensitivity that may contribute to clinical pain. In spinal pain, however, the relationship between sensory hypersensitivity and clinical pain remains unclear. This systematic review examined the relationship between pain sensitivity measured via quantitative sensory testing (QST) and self-reported pain or pain-related disability in people with spinal pain. ⋯ Fair correlations were found for the relationship between pain intensity and thermal temporal summation (0.26, 95% CI: 0.09 to 0.42) or pain tolerance (-0.30, 95% CI: -0.45 to -0.13), but only a few studies were available. Our study indicates either that pain threshold is a poor marker of central sensitization or that sensitization does not play a major role in patients' reporting of pain and disability. Future research prospects are discussed.
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Randomized Controlled Trial Multicenter Study
A phase 2, double-blind, randomized, placebo-controlled, dose-escalation study to evaluate the efficacy, safety, and tolerability of naloxegol in patients with opioid-induced constipation.
Naloxegol (previously known as NKTR-118) is a peripherally acting μ-opioid receptor antagonist engineered using polymer conjugate technology in development as an oral, once-daily agent for the treatment of opioid-induced constipation (OIC). Eligible patients with OIC (n=207), defined as <3 spontaneous bowel movements (SBMs) per week with accompanying symptoms, on a stable opioid regimen of 30-1000 mg/day morphine equivalents for ≥ 2 weeks were randomized to receive 4 weeks of double-blind placebo or naloxegol (5, 25, or 50mg) once daily in sequential cohorts after a 1-week placebo run-in. The primary end point, median change from baseline in SBMs per week after week 1 of drug administration, was statistically significant for the 25- and 50-mg naloxegol cohorts vs placebo (2.9 vs 1.0 [P=0.0020] and 3.3 vs 0.5 [P=0.0001], respectively). ⋯ Similar AEs occurred with increased frequency and severity in the 50-mg cohort. There was no evidence of a statistically significant increase from baseline in pain, opioid use for the 25- and 50-mg cohorts, or centrally mediated opioid withdrawal signs and/or symptoms with naloxegol. These data demonstrate that once-daily oral naloxegol improves the frequency of SBMs compared with placebo and is generally well tolerated in this population of patients with OIC.
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The lack of efficacy of rehabilitative approaches to the management of chronic whiplash-associated disorders (WAD) may be in part due to heterogeneity of the clinical presentation of this patient population. The aim of this study was to identify homogeneous subgroups of patients with chronic WAD on the basis of symptoms of PTSD and sensory hypersensitivity and to compare the clinical presentation of these subgroups. Successive k-means cluster analyses using 2, 3 and 4 cluster solutions were performed by using data for 331 (221 female) patients with chronic (>3 months) WAD. ⋯ The nPnH cluster was the largest cluster, comprising 43.5% of the sample. The PH cluster had significantly worse disability, pain intensity, self-reported mental health status and cervical range of motion in comparison to the nPnH and nPH clusters. These data provide further evidence of the heterogeneity of the chronic WAD population and the association of a more complex clinical presentation with higher disability and pain in this patient group.