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The United States is in the midst of an opioid overdose epidemic, with a significant portion of the burden associated with prescription opioids. In response, the CDC released a Guideline for Prescribing Opioids for Chronic Pain, which promotes access to treatment for opioid use disorder. Decades of research have linked childhood adversity to negative health and risk behavior outcomes, including substance misuse. Our present study builds upon this work to examine the relationship between adverse childhood experiences (ACEs) and prescription opioid misuse. We compiled data from the Behavioral Risk Factor Surveillance System implemented by Montana and Florida in 2010 and 2011, respectively. Logistic regressions (run in 2017) tested the associations between ACEs and subsequent prescription pain medicine/opioid misuse outcomes in adulthood. ACEs were prevalent, with 62.7% of respondents in Montana and 50% in Florida reporting at least one ACE. The presence of ACEs was positively associated with prescription opioid misuse across both samples. Respondents reporting three or more ACEs had increased odds of taking opioids more than prescribed, without a prescription, and for the feeling they cause. Our results support a strong link between ACEs and prescription opioid misuse. Opportunities to prevent opioid misuse start with assuring safe, stable, nurturing relationships and environments in childhood and across the lifespan to prevent ACEs from occurring, and intervening appropriately when they do occur. Substance use prevention programs for adolescents, appropriate pain management and opioid prescribing protocols, and treatments for opioid use disorder can address ACEs by enhancing treatment safety and effectiveness and can reduce the intergenerational continuity of early adversity.
Learn More >Despite the high prevalence of neck pain, few studies have addressed the pharmacological treatment of this condition. We evaluated the effectiveness of tapentadol prolonged-release (PR) in patients with or without a neuropathic pain component, with a focus on functional movements, disability and Quality of Life (QoL). Observational, retrospective study. Ninety-four adult patients with severe neck pain not responsive to opioid step III treatment. The primary endpoint was a ≥30% improvement of pain intensity at 4 weeks (W4). Several secondary outcomes were evaluated, including neck disability index (NDI), range of motion (ROM), and QoL. Patients received tapentadol PR at the starting dose of 100 mg/day. Dose titration was allowed in 50 mg increments, up to 500 mg daily. At W4, the primary endpoint of ≥30% improvement of pain was reported in 70% (n = 35; 95% confidence interval [CI]: 55-82%) of patients with a neuropathic pain component and in 69% (n = 20; 95% CI: 49-85%) of those without a neuropathic component. The percentage of patients reporting a neuropathic pain component significantly decreased from baseline (64.2%) to W4 (27.8%). NDI significantly improved in both groups at W12. ROM significantly improved in all three planes of motion (P < 0.01), with no difference between the two groups. Interference of pain with sleep and QoL also improved. The reduction in pain provided by tapentadol is associated with functional recovery, which may in turn be linked to an improvement in QoL.
Learn More >Slow deep breathing (SDB) is commonly employed in the management of pain, but the underlying mechanisms remain equivocal. This study sought to investigate effects of instructed breathing patterns on experimental heat pain and to explore possible mechanisms of action. In a within-subject experimental design, healthy volunteers (n = 48) performed four breathing patterns: 1) unpaced breathing (UB), 2) paced breathing at the participant's spontaneous breathing frequency (PB), 3) SDB at six breaths per minute with a high inspiration/expiration ratio (SDB-H), and 4) SDB at six breaths per minute with a low inspiration/expiration ratio (SDB-L). During presentation of each breathing pattern, participants received painful heat stimuli of three different temperatures and rated each stimulus on pain intensity. Respiration, heart rate, and blood pressure were recorded. Compared to UB, participants reported less intense pain during each of the three instructed breathing patterns. Among the instructed breathing patterns, pain did not differ between PB and SDB-H, and SDB-L attenuated pain more than the PB and SDB-H patterns. The latter effect was paralleled by greater blood pressure variability and baroreflex effectiveness index during SDB-L. Cardiovascular changes did not mediate the observed effects of breathing patterns on pain. Perspective: SDB is more efficacious to attenuate pain when breathing is paced at a slow rhythm with an expiration that is long relative to inspiration, but the underlying mechanisms remain to be elucidated.
Learn More >There is a major unmet need to develop new therapies for migraine. We have previously demonstrated the therapeutic potential of the acid sensing ion channel (ASIC) blockade in migraine, via an ASIC1 mechanism. ASIC3 is expressed in the trigeminal ganglion and its response is potentiated by nitric oxide that can trigger migraine attacks in patients, and thus we sought to explore the potential therapeutic effect of ASIC3 blockade in migraine.
Learn More >C-LTMRs are known to convey affective aspects of touch and to modulate injury-induced pain in humans and mice. However, a role for these neurons in temperature sensation has been suggested, but not fully demonstrated. Here, we report that deletion of C-low-threshold mechanoreceptor (C-LTMR)-expressed bhlha9 causes impaired thermotaxis behavior and exacerbated formalin-evoked pain in male, but not female, mice. Positive modulators of GABA receptors failed to relieve inflammatory formalin pain and failed to decrease the frequency of spontaneous excitatory post-synaptic currents (sEPSCs) selectively in bhlha9 knockout (KO) males. This could be explained by a drastic change in the GABA content of lamina II inner inhibitory interneurons contacting C-LTMR central terminals. Finally, C-LTMR-specific deep RNA sequencing revealed more genes differentially expressed in male than in female bhlha9 KO C-LTMRs. Our data consolidate the role of C-LTMRs in modulation of formalin pain and provide in vivo evidence of their role in the discriminative aspects of temperature sensation.
Learn More >For patients with painful chronic pancreatitis, surgical treatment is postponed until medical and endoscopic treatment have failed. Observational studies have suggested that earlier surgery could mitigate disease progression, providing better pain control and preserving pancreatic function.
Learn More >Postoperative pain relief is crucial for full recovery. With the ongoing opioid epidemic and the insufficient effect of acetaminophen on severe pain; non-steroidal anti-inflammatory drugs (NSAIDs) are heavily used to alleviate this pain. However, NSAIDs are known to inhibit postoperative healing of connective tissues by inhibiting prostaglandin signaling. Pain intensity, inflammatory mediators associated with wound healing and the pharmacological action of NSAIDs vary throughout the day due to the circadian rhythm regulated by the clock genes. According to this rhythm, most of wound healing mediators and connective tissue formation occurs during the resting phase, while pain, inflammation and tissue resorption occur during the active period of the day. Here we show, in a murine tibia fracture surgical model, that NSAIDs are most effective in managing postoperative pain, healing and recovery when drug administration is limited to the active phase of the circadian rhythm. Limiting NSAID treatment to the active phase of the circadian rhythm resulted in overexpression of circadian clock genes, such as Period 2 (Per2) at the healing callus, and increased serum levels of anti-inflammatory cytokines interleukin-13 (IL-13), interleukin-4 (IL-4) and vascular endothelial growth factor. By contrast, NSAID administration during the resting phase resulted in severe bone healing impairment.
Learn More >Prolonged endoplasmic reticulum stress has been identified in various diseases. Inflammatory mediators, which have been shown to induce endoplasmic reticulum stress in several studies, have been suggested to serve as the important modulators in pain development. In this study, the authors hypothesized that the endoplasmic reticulum stress triggered by inflammatory mediators contributed to pain development.
Learn More >Given the unknown immediate impact of migraine on nighttime sleep, we prospectively examined whether migraine headaches were associated with subsequent shorter sleep duration, higher fragmentation and poorer quality in a cohort of 98 adults with episodic migraine.
Learn More >A growing body of evidence has indicated that the release of nociceptive factors, such as interleukins and chemokines, by activated immune and glial cells has crucial significance for neuropathic pain generation and maintenance. Moreover, changes in the production of nociceptive immune factors are associated with low opioid efficacy in the treatment of neuropathy. Recently, it has been suggested that CC chemokine receptor type 1 (CCR1) signaling is important for nociception. Our study provides evidence that the development of hypersensitivity in rats following chronic constriction injury (CCI) of the sciatic nerve is associated with significant upregulation of endogenous CCR1 ligands, namely, CCL2, CCL3, CCL4, CCL6, CCL7 and CCL9 in the spinal cord and CCL2, CCL6, CCL7 and CCL9 in dorsal root ganglia (DRG). We showed that single and repeated intrathecal administration of J113863 (an antagonist of CCR1) attenuated mechanical and thermal hypersensitivity. Moreover, repeated administration of a CCR1 antagonist enhanced the analgesic properties of morphine and buprenorphine after CCI. Simultaneously, repeated administration of J113863 reduced the protein levels of IBA-1 in the spinal cord and MPO and CD4 in the DRG and, as a consequence, the level of pronociceptive factors, such as IL-1beta, IL-6, and IL-18. The obtained data provide evidence that CCR1 blockade reduces hypersensitivity and increases opioid-induced analgesia through the modulation of neuroimmune interactions.
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