Pain
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Blinding is challenging in randomised controlled trials of physical, psychological, and self-management therapies for pain, mainly because of their complex and participatory nature. To develop standards for the design, implementation, and reporting of control interventions in efficacy and mechanistic trials, a systematic overview of currently used sham interventions and other blinding methods was required. Twelve databases were searched for placebo or sham-controlled randomised clinical trials of physical, psychological, and self-management treatments in a clinical pain population. ⋯ We also provide an overview of additional, potentially useful methods to enhance blinding, as well as the reporting of processes involved in developing control interventions. A comprehensive picture of prevalent blinding methods is provided, including a detailed assessment of the resemblance between active and control interventions. These findings can inform future developments of control interventions in efficacy and mechanistic trials and best-practice recommendations.
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Clinical Trial
Capsaicin treatment in neuropathic pain: axon reflex vasodilatation after four weeks correlates with pain reduction.
Capsaicin, an agonist at the transient receptor potential vanilloid 1, is used for the topical treatment of peripheral neuropathic pain. Reversible receptor defunctionalization and degeneration and subsequent regeneration of cutaneous nociceptors are discussed as its mechanism of action. Here, we hypothesize an accelerated functional recovery of a subclass of nociceptive afferents, the peptidergic vasoactive nociceptors, as the potential cause of capsaicin analgesia. ⋯ Patients with improved heat-evoked neurogenic vasodilatation at week 4 showed a greater pain reduction than those with deterioration. The degree of vasodilatation significantly correlated with pain reduction. These findings suggest that (1) regeneration of peptidergic nociceptors may be the mechanism behind capsaicin-induced analgesia and (2) that a disease-modifying effect of capsaicin on these fibers already occurs 4 weeks after application.
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Pain is an alarm mechanism to prevent body damage in response to noxious stimuli. The nerve growth factor (NGF)/TrkA axis plays an essential role as pain mediator, and several clinical trials using antibodies against NGF have yielded promising results, but side effects have precluded their clinical approval. A better understanding of the mechanism of NGF/TrkA-mediated nociception is needed. ⋯ Simultaneous deletion of brain-derived neurotrophic factor (BDNF) reversed the effects of ARMS/Kidins220 knock down alone. Mechanistically, ARMS/Kidins220 levels are reduced in vitro and in vivo in response to capsaicin through calpains, and this reduction leads to enhanced regulated BDNF secretion from dorsal root ganglion. Altogether, these data indicate that ARMS/Kidins220 protein levels have a role as a pain modulator in the NGF/TrkA axis regulating BDNF secretion.
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Current research indicates that spinal cord stimulation (SCS) has a positive short-term impact on outcomes, such as quality of life, pain, and productivity in patients with chronic neuropathic pain. However, there is a need for studies on larger population samples. This study used data from Swedish national registers to analyze change and predictors of sick leave and disability pension 2 years before and after SCS treatment. ⋯ Large work loss prior to index date was also demonstrated (average 214 days before 1 year), indicating a significant burden on the patient, employers, and the society at large. The number of disability days varied considerably depending on age, sex, socioeconomic variables, and comorbidities; however, the effect of SCS seemed to have little association with patient characteristics. This economic benefit needs to be considered, as well as the clinical outcome, when evaluating the full societal value of SCS.
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Human epidemiological studies suggest that chronic pain can increase mortality risk. We investigated whether this was true in mice so that underlying mechanisms might be identified. At 10 weeks of age, C57BL/6 mice of both sexes received sham or spared nerve injury (SNI) surgery producing neuropathic pain. ⋯ However, in male mice with SNI, we observe a significant correlation between average lifetime mechanical hypersensitivity and lifespan, such that death occurred sooner in male mice exhibiting more evidence of chronic pain. This relationship was not observed in female SNI mice nor in sham-operated mice of either sex. This experiment is the first to investigate pain behavior over an entire adult lifetime and suggests that biology of relevance to human chronic pain is being ignored by the very short timespans of most extant preclinical pain research.