Browse by Audience
There is growing interest in the potential of internet-delivered pain management programs (PMPs) to increase access to care for people with chronic pain. However, very few economic evaluations of these interventions have been reported. Using existing data, the current study examined the cost-effectiveness of an internet-delivered PMP for a mixed group chronic pain patients (n = 490) provided with different levels of clinician support. The findings indicated that each additional clinical outcome (defined as a ≥ 30% reduction in disability, depression, anxiety and pain) was associated with cost-savings when the intervention was provided in a self-guided format (ICER range: -$404 to -$808 AUD) or an optional-guided format (ICER range: -$314 to -$541 AUD), and a relatively small fixed cost when provided in the clinician-guided format (ICER range: $88 to $225 AUD). The results were driven by a reduction in service use costs among the treatment groups, which offset the costs of providing the internet-delivered PMP in the self-guided and optional-guided formats. The same general pattern of results was found when more stringent clinical outcomes (defined as a ≥ 50% reduction) were employed. These findings suggest that carefully developed and administered internet-delivered PMPs, provided with different levels of clinician support, can be highly cost effective for patients with a broad range of pain conditions. PERSPECTIVE: This study examines the cost-effectiveness of an internet-delivered pain management program provided to adults with a broad range of chronic pain conditions. Evidence of cost-effectiveness was found across a broad range of clinical outcomes and with different levels of clinician support.
Learn More >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 (CIPN) 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. Our case series suggested that topical 10% amitriptyline treatment was associated with pain relief in CIPN patients, without the side effects associated with systemic absorption. Topical amitriptyline significantly increased mechanical withdrawal thresholds when applied to the hind paw of mice, and inhibited the firing responses of C-, Aβ- and Aδ-type peripheral nerve fibers in ex vivo skin-saphenous nerve preparations. Whole-cell patch-clamp recordings on cultured sensory neurons revealed that amitriptyline was a potent inhibitor of the main voltage-gated sodium channels (Nav1.7, Nav1.8 and Nav1.9) found in nociceptors. Calcium imaging showed that amitriptyline activated the transient receptor potential cation channel, TRPA1. Our case series indicated that high-dose 10% topical amitriptyline could alleviate neuropathic pain without adverse local or systemic effects. 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.
Learn More >Pain is a common but potentially debilitating symptom, often requiring complex management strategies. To understand the molecular dynamics of peripheral inflammation and nociceptive pain, we investigated longitudinal changes in behavior, tissue structure, and transcriptomic profiles in the rat carrageenan-induced peripheral inflammation model. Sequential changes in the number of differentially expressed genes are consistent with temporal recruitment of key leukocyte populations, mainly neutrophils and macrophages with each wave being preceded by upregulation of the cell-specific chemoattractants, Cxcl1 and Cxcl2, and Ccl2 and Ccl7, respectively. We defined 12 temporal gene clusters based on expression pattern. Within the patterns we extracted genes comprising the inflammatory secretome and others related to nociceptive tissue remodeling and to sensory perception of pain. Structural tissue changes, involving upregulation of multiple collagens occurred as soon as 1-hour post-injection, consistent with inflammatory tissue remodeling. Inflammatory expression profiling revealed a broad-spectrum, temporally orchestrated molecular and cellular recruitment process. The results provide numerous potential targets for modulation of pain and inflammation. PERSPECTIVE: This study investigates the highly orchestrated biological response during tissue inflammation with precise assessment of molecular dynamics at the transcriptional level. The results identify transcriptional changes that define an evolving inflammatory state in rats. This study provides foundational data for identifying markers of, and potential treatments for, inflammation and pain in patients.
Learn More >There is wide discrepancy on how to perform clinical assessment of oxaliplatin-induced peripheral neuropathy. In this scenario, the Electronic von Frey (EVF), which evaluates pain objectively based upon mechanical pain thresholds (MPTs), may be a valuable tool. The present study aims to quantify hyperalgesia in the hands and feet of patients treated with oxaliplatin and to propose a novel method to classify the degree of neurotoxicity using EVF-derived measures as cut-off points.
Learn More >The pharmacodynamics of opioids for chronic peripheral neuropathic pain are complex and likely extend beyond classical opioid receptor theory. Preclinical evidence of opioid modulation of central immune signalling has not been identified in vivo in humans. Examining the cerebrospinal fluid (CSF) of patients medicated with opioids is required to identify potential pharmacodynamic mechanisms. We compared CSF samples of chronic peripheral neuropathic pain patients receiving opioids (n = 7) versus chronic peripheral neuropathic pain patients not taking opioids (control group, n = 13). Baseline pain scores with demographics were recorded. Proteome analysis was performed using mass spectrometry and secreted neuropeptides were measured by enzyme-linked immunosorbent assay. Based on Gene Ontology analysis, proteins involved in the positive regulation of nervous system development and myeloid leukocyte activation were increased in patients taking opioids versus the control group. The largest decrease in protein expression in patients taking opioids were related to neutrophil mediated immunity. In addition, notably higher expression levels of neural proteins (85%) and receptors (80%) were detected in the opioid group compared to the control group. This study suggests modulation of CNS homeostasis, possibly attributable to opioids, thus highlighting potential mechanisms for the pharmacodynamics of opioids. We also provide new insights into the immunomodulatory functions of opioids in vivo.
Learn More >Nerve growth factor (NGF) is a neurotrophin that activates nociceptive neurons to transmit pain signals from the peripheral to the central nervous system and that exerts its effects on neurons by signalling through tyrosine kinase receptors. Antibodies that inhibit the function of NGF and small molecule inhibitors of NGF receptors have been developed and tested in clinical studies to evaluate the efficacy of NGF inhibition as a form of analgesia in chronic pain states including osteoarthritis and chronic low back pain. Clinical studies in individuals with painful knee and hip osteoarthritis have revealed that NGF inhibitors substantially reduce joint pain and improve function compared with NSAIDs for a duration of up to 8 weeks. However, the higher tested doses of NGF inhibitors also increased the risk of rapidly progressive osteoarthritis in a small percentage of those treated. This Review recaps the biology of NGF and the studies that have been performed to evaluate the efficacy of NGF inhibition for chronic musculoskeletal pain states. The adverse events associated with NGF inhibition and the current state of knowledge about the mechanisms involved in rapidly progressive osteoarthritis are also discussed and future studies proposed to improve understanding of this rare but serious adverse event.
Learn More >Neuropathic pain often accompanies the functional deficits associated with spinal cord injury (SCI) and further reduces a patient's quality of life. Clinical and pre-clinical research is beginning to highlight the beneficial role that rehabilitative therapies such as locomotor training can have not only on functional recovery but also on chronic pain management. Our group has previously developed an intensive locomotor training (ILT) treadmill protocol in a rat that reduced SCI neuropathic pain symptoms for at least 3 months. We have extended these findings in the current study to evaluate the ability of regular ILT regimen over a 2 year period post-SCI to maintain neuropathic pain reduction. To assess this, the rat clip compression SCI model (T7/8) was used and treadmill training initiated starting 4 weeks after SCI and continuing through the duration of the study. Results showed continued suppression of SCI neuropathic pain responses (reduced mechanical, heat, and cold hypersensitivity throughout the entire time course of the study. In contrast, non-exercised rats showed consistent and sustained neuropathic pain responses during this period. In addition, prolonged survival and improved locomotor outcomes were observed in rats undergoing ILT as the study longevity progressed. Potential contributory mechanisms underlying beneficial effects of ILT include reduced inflammation and restoration of antinociceptive inhibitory processes as indicated by neurochemical assays in spinal tissue of remaining rats at 2 years post-SCI. The benefits of chronic ILT suggest long-term physical exercise therapy can produce powerful and prolonged management of neuropathic pain, partly through sustained reduction of spinal pathological processes.
Learn More >To improve understanding of current practices in the treatment of children and adolescents with chronic pain in Spain.
Learn More >Map the current literature investigating autonomy development, identity development, and peer relationships in young people aged 10-24 years with chronic pain.
Learn More >