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Postherpetic neuralgia (PHN) is a common, complex, and refractory type of neuropathic pain. Several systematic reviews support the efficacy of acupuncture and related treatments for PHN. Nevertheless, the efficacy of various acupuncture-related treatments for PHN remains debatable.
Learn More >Neuropathic pain is a refractory disease that occurs across the world and pharmacotherapy has limited efficacy and/or safety. This disease imposes a significant burden on both the somatic and mental health of patients; indeed, some patients have referred to neuropathic pain as being 'worse than death'. The pharmacological agents that are used to treat neuropathic pain at present can produce mild effects in certain patients, and induce many adverse reactions, such as sedation, dizziness, vomiting, and peripheral oedema. Therefore, there is an urgent need to discover novel drugs that are safer and more effective. Natural compounds from medical plants have become potential sources of analgesics, and evidence has shown that glycosides alleviated neuropathic pain via regulating oxidative stress, transcriptional regulation, ion channels, membrane receptors and so on. In this review, we summarize the epidemiology of neuropathic pain and the existing therapeutic drugs used for disease prevention and treatment. We also demonstrate how glycosides exhibit an antinociceptive effect on neuropathic pain in laboratory research and describe the antinociceptive mechanisms involved to facilitate the discovery of new drugs to improve the quality of life of patients experiencing neuropathic pain.
Learn More >Оligoarginines were recently discovered (Lebedev et al., 2019 Nov) [1] as a novel class of nicotinic acetylcholine receptors (nAChRs) inhibitors, octaoligoarginine R8 showing a relatively high affinity (40 nM) for the α9/α10 nAChR. Since the inhibition of α9/α10 nAChR by α-conotoxin RgIA and its analogs is a possible way to drugs against neuropathic pain, here in a mice model we compared R8 with α-conotoxin RgIA in the effects on the chemotherapy-induced peripheral neuropathy (CIPN), namely on the long-term oxaliplatin induced neuropathy. Tests of cold allodynia, hot plate, Von Frey and grip strength analysis revealed for R8 and α-conotoxin RgIA similar positive effects, expressed most prominently after two weeks of administration. Histological analysis of the dorsal root ganglia sections showed for R8 and RgIA a similar partial correction of changes in the nuclear morphology of neurons. Since α9/α10 nAChR might be not the only drug target for R8, we analyzed the R8 action on rat TRPV1 and TRPA1, well-known nociceptive receptors. Against rTRPV1 at 25 μM there was no inhibition, while for rTRPA1 IC was about 20 μM. Thus, involvement of rTRPA1 cannot be excluded, but in view of the R8 much higher affinity for α9/α10 nAChR the latter seems to be the main target and the easily synthesized R8 can be considered as a potential candidate for a drug design.
Learn More >C-shapes are stereotyped movements in planarians that are elicited by diverse stimuli (e.g. acidity, excitatory neurotransmitters, psychostimulants, and pro-convulsants). Muscle contraction and seizure contribute to the expression of C-shape movements, but a causative role for pain is understudied and unclear. Here, using nicotine-induced C-shapes as the endpoint, we tested the efficacy of three classes of antinociceptive compounds – an opioid, NSAID (non-steroidal anti-inflammatory drug), and transient receptor potential ankyrin 1 (TRPA1) channel antagonist. For comparison we also tested effects of a neuromuscular blocker. Nicotine (0.1-10 mM) concentration-dependently increased C-shapes. DAMGO (1-10 µM), a selective µ-opioid agonist, inhibited nicotine (5 mM)-induced C-shapes. Naloxone (0.1-10 µM), an opioid receptor antagonist, prevented the DAMGO (1 µM)-induced reduction of nicotine (5 mM)-evoked C-shapes, suggesting an opioid receptor mechanism. C-shapes induced by nicotine (5 mM) were also reduced by meloxicam (10-100 µM), a NSAID; HC 030031 (1-10 µM), a TRPA1 antagonist; and pancuronium (10-100 µM), a neuromuscular blocker. Evidence that nicotine-induced C-shapes are reduced by antinociceptive drugs from different classes, and require opioid receptor and TRPA1 channel activation, suggest C-shape etiology involves a pain component.
Learn More >Endometriosis is a difficult to manage condition associated with a significant disease burden. High levels of illicit cannabis use for therapeutic purposes have been previously reported by endometriosis patients in Australia and New Zealand (NZ). Although access to legal medicinal cannabis (MC) is available through medical prescription via multiple federal schemes, significant barriers to patient access remain. An anonymous cross-sectional online survey was developed and distributed through social media via endometriosis advocacy groups worldwide. Respondents were asked about legal versus illicit cannabis usage, their understanding of access pathways and legal status, and their interactions with health care professionals. Of 237 respondents who reported cannabis use with a medical diagnosis of endometriosis, 186 (72.0%) of Australian and 51 (88.2%) NZ respondents reported self-administering cannabis illicitly. Only 23.1% of Australian and 5.9% of NZ respondents accessed cannabis through a doctor's prescription, with 4.8% of Australian and no NZ respondents reporting to legally self-administer cannabis. Substantial substitution effects (>50% reduction) were observed in users of nonopioid analgesia (63.1%), opioid analgesia (66.1%), hormonal therapies (27.5%), antineuropathics (61.7%), antidepressants (28.2%) and antianxiety medications (47.9%). Of Australian respondents, 18.8% and of NZ respondents, 23.5% reported not disclosing their cannabis use to their medical doctor, citing concern over legal repercussions, societal judgment, or their doctors' reaction and presumed unwillingness to prescribe legal MC. Respondents self-reported positive outcomes when using cannabis for management of endometriosis, demonstrating a therapeutic potential for MC. Despite this, many are using cannabis without medical supervision. While evidence for a substantial substitution effect by cannabis was demonstrated in these data, of particular concern are the clinical consequences of using cannabis without medical supervision, particularly with regard to drug interactions and the tapering or cessation of certain medications without that supervision. Improving doctor and patient communication about MC use may improve levels of medical oversight, the preference for legal MC adoption over acquisition via illicit supply and reducing cannabis-associated stigma.
Learn More >Blood nerve barrier (BNB) disruption and edema are common in neuropathic pain as well as complex regional pain syndrome (CRPS). MicroRNAs (miRNA) are epigenetic multitarget switches controlling neuronal and non-neuronal cells in pain. The miR-183 complex attenuates hyperexcitability in nociceptors, but additional non-neuronal effects via transcription factors could contribute as well. This study explored exosomal miR-183 in CRPS and murine neuropathy, its effect on the microvascular barrier via transcription factor FoxO1 and tight junction protein claudin-5, and its antihyperalgesic potential. Sciatic miR-183 decreased after CCI. Substitution with perineural miR-183 mimic attenuated mechanical hypersensitivity and restored BNB function. In vitro, serum from CCI mice und CRPS patients weakened the microvascular barrier of murine cerebellar endothelial cells, increased active FoxO1 and reduced claudin-5, concomitant with a lack of exosomal miR-183 in CRPS patients. Cellular stress also compromised the microvascular barrier which was rescued either by miR-183 mimic via FoxO1 repression or by prior silencing of Foxo1. Perspective: Low miR-183 leading to barrier impairment via FoxO1 and subsequent claudin-5 suppression is a new aspect in the pathophysiology of CRPS and neuropathic pain. This pathway might help untangle the wide symptomatic range of CRPS and nurture further research into miRNA mimics or FoxO1 inhibitors.
Learn More >People with chronic pain engage in various strategies, such as pain catastrophizing and pain acceptance, to regulate the difficult emotional aspects of living with pain. Engagement in these strategies is known to influence pain severity and pain interference. However, less research has examined the extent to which general emotion regulation, the ability to identify emotions and engage in strategies to alter emotions, relates to pain-related outcomes. The current study, a large (N = 1453) online prospective study of adults with chronic pain, employed theory-driven assessment of emotion regulation to determine the extent to which general difficulties with emotion regulation at baseline relate to pain severity and pain interference at three-month follow-up, above and beyond pain catastrophizing and pain acceptance. We conducted a series of path models, controlling for demographic covariates and baseline pain severity and pain interference. Pain catastrophizing and pain acceptance at baseline significantly predicted pain interference at three-month follow-up. However, when indices of general emotion regulation were entered into the model, the associations between pain catastrophizing and pain interference (B = .009, p = .153) were no longer statistically significant. Alexithymia emerged as a significant predictor of pain severity (B = .012, p = .032) and pain interference (B = .026, p < .001). These findings highlight the value of considering the role of general emotion regulation (particularly identifying and describing emotions), in addition to pain-specific experiences, in understanding risk for poor pain-related outcomes. PERSPECTIVE: : In addition to pain catastrophizing and pain acceptance, difficulties regulating emotions in general (particularly elevated alexithymia) relates to pain outcomes three months later. These findings shed light on risk for poor pain outcomes and point to general emotion regulation as a potentially important target of chronic pain intervention.
Learn More >Studies have identified high rates of chronic postsurgical pain in adolescents. Characterizing patterns of pain in the transition from acute to chronic following major surgery may pinpoint critical periods of recovery. This observational study modelled pain trajectories over 1-year following surgery to attempt replication of prior work and evaluate baseline psychosocial factors and 12-month health outcomes. Adolescents 10-18 years completed electronic daily pain reporting for 7 days and self-reported health outcomes, at 5 assessment timepoints. Group-based trajectory modelling identified two trajectories with similar starting points in-hospital but distinct recovery courses at home. Pain declined steadily in one group across the study period ("Declining Pain"; estimated probability,18.9%), but pain increased after hospital discharge and remained high through 12-months in the other group ("High and Persistent Pain"; estimated probability,81.1%). Pre-surgery pain (aOR=1.86,p=0.001) and sleep quality (aOR=0.49,p=0.029) were associated with the High and Persistent pain trajectory in multivariate regressions. This trajectory was associated with lower total quality of life (B=-9.79,p=0.002), physical health (B=-15.93,p<0.001), psychosocial health (B=-6.73,p=0.06), and greater fatigue (B=-13.61,p=0.001). This study replicated prior findings identifying two post-surgical pain trajectories with diverging pain in the first two weeks. Clinical detection of those with increasing pain and early intervention may interrupt persistence of pain. PERSPECTIVE: . This article replicates a prior study identifying distinct post-surgical pain trajectories, Declining Pain and High and Persistent Pain. The High and Persistent pain trajectory is associated with pre-surgery pain, pre-surgery sleep quality, and lower quality of life (total, physical, and psychosocial health as well as fatigue) at 12-month follow-up.
Learn More >To address the ongoing opioid epidemic, there has been an increased focus on the treatment and evaluation of opioid use disorder (OUD). OUD and chronic pain (CP) frequently co-occur; however, little is known about the additional comorbidities that present when they occur together as compared to when either condition presents alone. Using data from Fiscal Year 2012 Veteran's Health Administration, all veterans diagnosed with both OUD + CP were compared to those diagnosed with OUD or CP alone on socioenvironmental characteristics, medical and mental health diagnoses, and Veterans Affairs (VA) clinical service use. Veterans with OUD + CP ( = 33,166), compared to those with OUD only (n = 12,517), had higher numbers of medical conditions. Compared to those with CP only ( = 2,015,368), veterans with OUD + CP had higher rates of homelessness and substance use diagnoses. Most mental health diagnoses, numbers of psychotropic medication fills, opioid prescriptions, and use of all other services were higher in the OUD + CP group than in either single disorder group. Multinomial regression analysis revealed stronger effects for medical disorders and medical-surgical outpatient service use in the comparison of OUD + CP with OUD only and stronger effects for substance use and mental health disorders and use of prescription opiates in the comparison with CP only. These findings suggest that concurrent OUD + CP imposes exceptional disease and clinical service burdens that likely require the development of simultaneous, integrated approaches to treatment. (PsycInfo Database Record (c) 2021 APA, all rights reserved).
Learn More >To investigate the effects of a group-based cognitive behavioural intervention for patients with persistent low back pain (LBP) and psychological risk factors referred to secondary care.
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