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People report substituting cannabis for pain medications, but whether cannabidiol (CBD) is used similarly remains unknown. CBD products can be CBD alone (isolate), hemp extract (containing <0.3% Δ-9-tetrahydrocannabinol [THC], other cannabinoids, and terpenes), or CBD-cannabis (containing >0.3% THC). In a secondary analysis from a cross-sectional survey, we examined substitution patterns among n = 878 individuals with fibromyalgia who currently used CBD. We sub-grouped participants by most commonly used CBD product (CBD isolate, hemp, CBD-cannabis, no preference) and whether they substituted CBD for medications. We investigated rationale for substituting, substitution-driven medication changes, CBD use patterns, and changes in pain-related symptoms (e.g., sleep, anxiety). The study population was 93.6% female and 91.5% Caucasian, with an average age of 55.5 years. The majority (n = 632, 72.0%) reported substituting CBD products for medications, most commonly NSAIDs (59.0%), opioids (53.3%), gabapentanoids (35.0%), and benzodiazepines (23.1%). Most substituting participants reported decreasing or stopping use of these pain medications. The most common reasons for substitution were fewer side effects and better symptom management. Age, hemp products, past-year use of marijuana, and higher somatic burden were all associated with substituting (p's ≤ 0.05). Those who substituted reported larger improvements in health and pain than those who did not. Participants using CBD-cannabis reported significantly more substitutions than any other group (p's ≤ 0.001) and larger improvements in health, pain, memory, and sleep than other subgroups. This widespread naturalistic substitution for pain medications suggests the need for more rigorous study designs to examine this effect. Perspective: This article shows that people with fibromyalgia are deliberately substituting CBD products for conventional pain medications despite the dearth of evidence suggesting CBD products may be helpful for fibromyalgia. CBD's medication-sparing and therapeutic potential should be examined in more rigorous study designs.
Learn More >In patients with chronic pain, a relative lower parasympathetic activity is suggested based on heart rate variability measurements. It is hypothesized that spinal cord stimulation (SCS) is able to influence the autonomic nervous system. The aim of this study is to further explore the influence of SCS on the autonomic nervous system by evaluating whether SCS is able to influence skin conductance, blood volume pulse, heart rate, and respiration rate.
Learn More >N-acylethanolamine acid amidase (NAAA) is an N-terminal cysteine hydrolase that stops the physiological actions of palmitoylethanolamide (PEA), an endogenous lipid messenger that activates the transcription factor, peroxisome proliferator-activated receptor-α. We have previously reported that the compound ARN19702 ((2-ethylsulfonylphenyl)-[(2S)-4-(6-fluoro-1,3-benzothiazol-2-yl)-2-methylpiperazin-1-yl]methanone) is an orally active, reversible NAAA inhibitor (median inhibitory concentration, IC, on human NAAA = 230 nM) that produces remarkable protective effects against multiple sclerosis in mice. In the present study, we assessed the profile of ARN19702 in mouse and rat models of acute and neuropathic pain. Oral administration in male mice attenuated in a dose-dependent manner the spontaneous nocifensive response elicited by intraplantar formalin injection and the hypersensitivity caused by intraplantar carrageenan injection, paw incision or the sciatic nerve ligation. In male rats, ARN19702 reduced nociception associated with paclitaxel-induced neuropathy without development of sub-acute antinociceptive tolerance. Finally, ARN19702 (30 mg/kg, oral) did not produce place-preference or alter exploratory motor behavior in male mice. The findings support the conclusion that NAAA is a suitable molecular target for the discovery of efficacious analgesic drugs devoid of rewarding potential. We evaluated the pharmacological profile of the orally bioavailable NAAA inhibitor ARN19702 in mouse and rat models of neurogenic and inflammatory pain. The compound's potential rewarding and sedative effects were also examined. We conclude that ARN19702 exhibits a broad analgesic profile that can be generalized across rodent species. Our findings point to NAAA as a control node in the processing of neuropathic and inflammatory pain, and to ARN19702 as a lead to uncover novel pain therapeutics devoid of addictive potential.
Learn More >The objective of this overview is to discuss the development, implementation, data content, and structure of the Uniformed Services University Pain Registry Biobank. Additionally, procedures and policies for accessing samples for pain-related research purposes are detailed.
Learn More >There is increasing demand for prediction of chronic pain treatment outcomes using machine-learning models, in order to improve suboptimal pain management. In this exploratory study, we used baseline brain functional connectivity patterns from chronic pain patients suffering from Fibromyalgia (FM) to predict whether a patient would respond differentially to either milnacipran or pregabalin, two FDA-approved drugs for the treatment of FM.
Learn More >Long-term opioid treatment (L-TOT) of chronic non-cancer pain (CNCP) patients has been suspected to alter the endocrine system. This systematic review and meta-analysis aimed at investigating the published evidence of L-TOT effects on the endocrine system in adult CNCP patients.
Learn More >Atopic dermatitis(AD) causes sleep disturbance, yet the epidemiology is not known.
Learn More >A significant portion of individuals living with traumatic spinal cord injury (SCI) experiences some degree of debilitating neuropathic pain (NP). This pain remains largely intractable in a majority of cases, due in part to an incomplete understanding of its underlying mechanisms. Central sensitization, an increase in excitability of pain transmission neurons located in superficial dorsal horn (sDH), plays a key role in development and maintenance of SCI-induced NP. Resident microglia and peripheral monocyte-derived macrophages (referred to collectively as MMΦ) are involved in promoting SCI-induced DH neuron hyperexcitability. Importantly, these MMΦ consist of populations of cells that can exert pro-inflammatory or anti-inflammatory signaling within injured spinal cord. It is critical to spatiotemporally characterize this heterogeneity to understand MMΦ contribution to NP after SCI. Given that a majority of SCI cases are cervical in nature, we used a model of unilateral C5/C6 contusion that results in persistent at-level thermal hyperalgesia and mechanical allodynia, two forms of NP-related behavior, in the forepaw. The aim of this study was to characterize the sDH MMΦ response within intact cervical spinal cord segments caudal to the lesion (i.e. the location of primary afferent nociceptive input from the forepaw plantar surface). Cervical SCI promoted a persistent MMΦ response in sDH that coincided with the chronic NP phenotype. Using markers of pro- and anti-inflammatory MMΦ, we found that the MMΦ population within sDH exhibited significant heterogeneity that evolved over time post-injury, including a robust and persistent increase in pro-inflammatory MMΦ that was especially pronounced at later times. C5/C6 contusion SCI also induced below-level thermal hyperalgesia and mechanical allodynia in the hindpaw; however, we did not observe a pronounced MMΦ response in sDH of L4/L5 spinal cord, suggesting that different inflammatory cell mechanisms occurring in sDH may be involved in at-level versus below-level NP following SCI. In conclusion, our findings reveal significant MMΦ heterogeneity both within and across pain transmission locations after SCI. These data also show a prominent and persistent pro-inflammatory MMΦ response, suggesting a possible role in DH neuron hyperexcitability and NP.
Learn More >Postherpetic neuralgia (PHN) is the most common complication of acute herpes zoster. The treatment of PHN remains a challenge for clinical pain management. The present study investigated the P2X7 receptor antagonist brilliant blue G (BBG) whether inhibits endoplasmic reticulum stress and pyroptosis (a necrotic form of cell death) and alleviates PHN. Varicella zoster virus (VZV)-infected CV-1 cells were used to induce PHN model. Mechanical paw withdrawal thresholds were measured using an ascending series of von Frey filaments. Immunohistochemistry was used to detect the expression of P2X7R in nerve tissues. Western blot was used to determine the expression of endoplasmic reticulum (ER) stress and pyroptosis-related molecules. The expression of IL-1β and IL-18 in tissue homogenate was detected by ELISA. The PHN rat has the lower paw withdrawal threshold, but higher expression of P2X7 in nerve tissues. And, endoplasmic reticulum stress was activated and pyroptosis was increased in PHN rats. BBG can decrease pain thresholds and reduce ER stress and pyroptosis in PHN rats. In addition, ER stress activator tunicamycin (TM) can reverse the effect of BBG on the paw withdrawal thresholds, endoplasmic reticulum stress, and pyroptosis. Therefore, P2X7 receptor antagonist BBG alleviates PHN by activating ER stress and reducing pyroptosis.
Learn More >Neuropathic pain (NP) after spinal cord injury (SCI) is a disabling condition, without an effective treatment. Hyperexcitability of N-methyl-D-aspartate (NMDA) receptors and oxidative stress have been reported to be associated with pain development. Amantadine, a NMDA receptor antagonist, has been proposed as a potential therapy for NP. However, its use has not been tested for NP after SCI.
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