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New treatments for stress-related disorders including depression, anxiety and Substance Use Disorder are greatly needed. Kappa opioid receptors (KORs) are expressed in central nervous system, including areas implicated in analgesia and affective state. Although KOR agonists share the antinociceptive effects of mu opioid receptor (MOR) agonists, they also tend to produce negative affective states. In contrast, selective KOR antagonists have antidepressant- and anxiolytic-like effects, stimulating interest in their therapeutic potential. The prototypical KOR antagonists (e.g., norBNI, JDTic) have an exceptionally long duration of action that complicates their use in humans, particular in tests to establish safety. This study was designed to test dose- and time-course effects of novel KOR antagonists with the goal of identifying short-acting lead compounds for future medication development.
Learn More >Previous findings have demonstrated that torture survivors exhibit chronic pain and alterations in pain perception. However, not much is known regarding the characteristics of the torture experience and its contribution to these long-term ramifications. The current study examined the unique role of objective severity and subjective suffering in torture in predicting chronic pain and acute pain perception and pain modulation.
Learn More >Sensitivity-related trait characteristics involving physical and emotional sensitivities and high trait anxiety personality types have been observed in individuals with non-specific chronic low back pain (NSCLBP). High trait sensitivity to sensory stimulation combined with interpretation biases based on personality type may contribute to the development of central sensitisation (CS) symptoms. To date there is limited research that has considered both sensitivity levels and personality type in NSCLBP with CS. The purpose of this study was to investigate 1) relationships between trait sensory profiles, trait anxiety and CS symptoms, and 2) the predictive capacity of sensory profiles, trait anxiety and personality types on CS symptoms, in people with NSCLBP.
Learn More >Many recommended nonpharmacologic therapies for patients with chronic spinal pain require visits to providers such as acupuncturists and chiropractors. Little information is available to inform third-party payers' coverage policies regarding ongoing use of these therapies. This study offers contingent valuation-based estimates of patient willingness-to-pay (WTP) for pain reductions from a large (n=1583) sample of patients using ongoing chiropractic care to manage their chronic low-back and neck pain. Average WTP estimates were $45.98 (45.8) per month per 1-point reduction in current pain for chronic low-back pain and $37.32 (38.0) for chronic neck pain. These estimates met a variety of validity checks including that individuals' values define a downward-sloping demand curve for these services. Comparing these WTP estimates to patients' actual use of chiropractic care over the next 3 months indicates that these patients are likely "buying" perceived pain reductions from what they believe their pain would have been if they didn't see their chiropractor-i.e., they value maintenance of their current mild pain levels. These results provide some evidence for co-pay levels and their relationship to patient demand but call into question ongoing coverage policies that require documentation of continued improvement or of experienced clinical deterioration with treatment withdrawal. Perspective: This study provides estimates of reported willingness-to-pay for pain reduction from a large sample of patients using chiropractic care to manage their chronic spinal pain and compares these estimates to what these patients do for care over the next 3 months, to inform coverage policies for ongoing care.
Learn More >The number of unintentional deaths due to prescription drug overdose has risen in recent years due to the increased utilization of opioid analgesics. Pain is one of the most common reasons for patients to visit an emergency department (ED) and is often treated with opioid analgesics. In 2016, the Centers for Disease Control and Prevention (CDC) released guidelines for primary care providers on prescribing opioids for chronic pain.
Learn More >All patients with migraine merit acute treatment, which should optimally achieve a sustained pain-free response. Maximum acute treatment is associated with reduced risk of transformation of episodic to chronic migraine. The American Headache Society published the most recent complete evidence assessment of acute migraine treatments in 2015. Noninvasive neuromodulation represents a new, Food and Drug Administration-approved nonsignificant risk alternative for acute migraine therapy. The future of acute migraine treatment includes new devices and formulations of existing medications, new classes of acute medications, and new noninvasive nonsignificant risk neuromodulation devices, with many anticipated in the next few years.
Learn More >Most of the clinical characteristics of cluster headache (CH) have been established through the observation of men with CH. Epidemiological data of CH in women are scarce especially in the Asian population. Here, we sought to assess the prevalence and clinical characteristics of women with CH in comparison to men in a prospective CH registry.
Learn More >Post-herpetic neuralgia (PHN) is a well-established clinical problem with potential severe personal and socioeconomic implications. GTP cyclohydrolase 1 (GCH1) gene, which encodes the rate-limiting enzyme in tetrahydrobiopterin synthesis, has been strongly implicated to be associated with neuropathic pain in previous animal and human studies. The rs3783641 (T > A) single-nucleotide polymorphism (SNP) in the GCH1 gene is functional. Here we examine the association between rs3783641 and PHN. A total of 292 subjects including 103 PHN patients, 87 herpes zoster (HZ) patients and 102 healthy controls were enrolled in this study. The rs3783641 polymorphisms were detected via the high-resolution melting curve (HRM) method. There were statistical differences between PHN group and the other two groups in genotype distribution (P = 0.029 and 0.017, respectively) and allele frequency (P = 0.032 and 0.005, respectively) of rs3783641. The proportion of subjects with AA genotype in the PHN group was significantly lower compared to HZ group and control group (P = 0.026 and 0.016, respectively). The frequency of A allele was lower in the PHN group than in control group (P = 0.005), and the frequency of T allele in the PHN group was higher than in HZ group and control group (P = 0.001 and 0.003, respectively). The results of this study suggest that the rs3783641 SNP in the GCH1 gene is associated with PHN, and the AA genotype showed a protective effect in PHN.
Learn More >Couple interventions for chronic pain have been shown to more effectively reduce pain intensity for individuals with chronic pain (ICPs) than individual behavioral interventions or usual care. This systematic review identifies randomized controlled trials (RCTs) of couple interventions to highlight strategies that could be incorporated into psychotherapy with ICPs and their romantic partners.
Learn More >Neuropathic pain is chronic pain that follows nerve injury, mediated in the brain by elevated levels of the inflammatory protein tumor necrosis factor-alpha (TNF). We have shown that peripheral nerve injury increases TNF in the hippocampus/pain perception region, which regulates neuropathic pain symptoms. In this study we assessed pain sensation and perception subsequent to specific targeting of brain-TNF (via TNF antibody) administered through a novel subcutaneous perispinal route. Neuropathic pain was induced in Sprague-Dawley rats via chronic constriction injury (CCI), and thermal hyperalgesia was monitored for 10 days post-surgery. On day 8 following CCI and sensory pain behavior testing, rats were randomized to receive perispinal injection of TNF antibody or control IgG isotype antibody. Pain perception was assessed using conditioned place preference (CPP) to the analgesic, amitriptyline. CCI-rats receiving the perispinal injection of TNF antibody had significantly decreased CCI-induced thermal hyperalgesia the following day, and did not form an amitriptyline-induced CPP, whereas CCI-rats receiving perispinal IgG antibody experienced pain alleviation only in conjunction with i.p. amitriptyline and did form an amitriptyline-induced CPP. The specific targeting of brain TNF via perispinal delivery alleviates thermal hyperalgesia and positively influences the affective component of pain. Perspective This study presents a novel route of drug administration to target central TNF for treatment of neuropathic pain. Targeting central TNF through perispinal drug delivery could potentially be a more efficient and sustained method to treat patients with neuropathic pain.
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