The journal of pain : official journal of the American Pain Society
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Observational Study
Analgesic Effects of Topical Amitriptyline in Patients with Chemotherapy-Induced Peripheral Neuropathy: Mechanistic Insights from Studies in Mice.
Oral amitriptyline hydrochloride (amitriptyline) is ineffective against some forms of chronic pain and is often associated with dose-limiting adverse events. We evaluated the potential effectiveness of high-dose topical amitriptyline in a preliminary case series of chemotherapy-induced peripheral neuropathy patients and investigated whether local or systemic adverse events associated with the use of amitriptyline were present in these patients. We also investigated the mechanism of action of topically administered amitriptyline in mice. ⋯ This analgesic action appeared to be mediated through local inhibition of voltage-gated sodium channels. PERSPECTIVE: Our preliminary case series suggested that topical amitriptyline could provide effective pain relief for chemotherapy-induced peripheral neuropathy patients without any systemic or local adverse events. Investigation of the mechanism of this analgesic action in mice revealed that this activity was mediated through local inhibition of nociceptor Nav channels.
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Review Meta Analysis
Investigating the true effect of psychological variables measured prior to arthroplastic surgery on post-surgical outcomes: a p-curve analysis.
Patients' presurgical psychological profiles have been posited to predict pain and function following arthroplastic surgery of the hip and knee. Nevertheless, findings are conflicting, and this may be rooted in biased reporting that makes the determination of evidential value difficult. This ambiguity may have negative consequences for researchers and governmental agencies, as these rely on findings to accurately reflect reality. ⋯ The results highlight the importance of patients' psychological profiles in predicting surgical outcomes, which represent a promising avenue for future treatment approaches. PERSPECTIVE: The effects of P-hacking are difficult to detect and might be at the root of conflicting findings pertaining to the predictive properties of presurgical psychological variables on postsurgical outcomes. P-Curve analysis allows the determination of evidential value underlying these relationships and detection of P-hacking to ensure that findings are not the result of selective reporting.
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Randomized Controlled Trial
III. Detecting Treatment Effects in Clinical Trials With Different Indices of Pain Intensity Derived From Ecological Momentary Assessment.
Pain intensity represents the primary outcome in most pain clinical trials. Identifying methods to measure aspects of pain that are most sensitive to treatment may facilitate discovery of effective interventions. In this third of 3 articles examining alternative indices of pain intensity derived from ecological momentary assessments (EMA), we compare treatment effects based on Average Pain, Maximum Pain, Minimum Pain, Pain Variability, Time in High Pain, Time in Low Pain, and Pain After Wake-Up. ⋯ Results suggest that different pain indices could be used to detect treatment effects in pain clinical trials. PERSPECTIVE: Alternative summary measures of pain intensity derived from EMA may broaden the scope of outcomes useful in pain clinical trials. In this analysis of a pharmacological treatment for fibromyalgia, most pain summary measures indicated similar effects; improvements in Maximum Pain and Pain Variability contributed to understanding PGIC over Average Pain.
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Randomized Controlled Trial
Prior pain exposure and mere possession of a placebo analgesic predict placebo analgesia: Findings from a randomised, double-blinded, controlled trial.
A recent study found that merely possessing a placebo analgesic reduces pain. The current study tested for a possible moderator of this effect. Specifically, does the mere possession of a placebo analgesic affect pain for individuals with and without immediate prior experience with the pain task? Healthy participants (N = 127) were randomized to prior pain (PP) condition or without prior pain (No-PP) condition. ⋯ PERSPECTIVE: This article presents a novel finding that prior pain exposure and mere possession of a placebo analgesic predicted placebo analgesia. It offers a novel perspective on the time course of placebo effect. It provides practical implications on potential pain intervention for clinicians and paradigm design for researchers of placebo study.
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The rationale of spinal administration of endothelin-1(ET-1) mediated anti-nociceptive effect has not been elucidated. ET-1 is reported to promote nuclear effluxion of histone deacetylase 5 (HDAC5) in myocytes, and spinal HDAC5 is implicated in modulation of pain processing. In this study, we aimed to investigate whether central ET-1 plays an anti-nociceptive role by facilitating spinal HDAC5 nuclear shuttling under neuropathic pain. ⋯ Therefore, inducing spinal GABAergic neuronal HDAC5 nuclear exportation may be a novel therapeutic approach for managing neuropathic pain. PERSPECTIVE: Neuropathic pain is intractable in a clinical setting, and epigenetic regulation is considered to contribute to this processing. Characterizing the anti-nociceptive effect of ET-1 and investigating the associated epigenetic mechanisms in animal models may lead to the development of new therapeutic strategies and targets for treating neuropathic pain.