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Ketamine has recently emerged as a promising therapeutic alternative for abortive migraine therapy, likely secondary to N-methyl-d-aspartate antagonism. Most reports examine adults and the intravenous route. Fewer utilize intranasal administration or pediatric populations. Given the limited evidence for intranasal ketamine in pediatric migraine populations, we retrospectively reviewed our experience to further characterize safety and efficacy of intranasal ketamine in this population.
Learn More >Shoulder surgery is a primary intervention for shoulder pain, yet many individuals experience persistent post-operative pain. Previously, we found individuals categorized as having a high-risk phenotype (comprised of COMT variation and pain catastrophizing) had approximately double the chance of not reaching a 12-month pain recovery criterion. As a means to better understand the development of persistent post-operative shoulder pain, this study advanced our previous work by examining temporal ordering of post-operative shoulder recovery based on potential mediating factors, and expansion of outcomes to include movement-evoked pain and shoulder active range of motion. Before surgery, individuals were categorized as either high-risk (high pain catastrophizing, COMT-genotype linked to low enzyme activity (n=41)) or low-risk (low pain catastrophizing, COMT-genotype linked to normal enzyme activity (n=107)). We then compared potential mediating variables at 3, 6, and 12 months post-operatively: 1) endogenous pain modulation defined by a conditioned pain modulation paradigm (CPM); and 2) and emotion factors such as anxiety, fear of movement, and depressive symptoms. At 3 months, the high-risk subgroup had higher fear and movement-evoked pain, and causal mediation analysis confirmed the direct effect of risk subgroup on 12-month movement evoked pain. However, 12-month depressive symptoms were found to mediate 53% of the total effect of risk subgroup on 12-month movement-evoked pain. This study introduces potential temporal components and relationships to the development of persistent post-operative shoulder pain, which future studies will confirm and assess for potential therapeutic targets. Perspective: This study expands upon post-operative shoulder recovery measures to include movement-evoked pain and depressive symptoms, and provides preliminary indication of temporal ordering to post-operative shoulder recovery for a pre-identified high-risk subgroup. Future studies will distinguish temporal components of shoulder surgery that may optimize treatment targets of post-operative recovery.
Learn More >Improvements in the survival of breast cancer patients have led to the emergence of bone health and pain management as key aspects of patient's quality of life. Here, we used a female rat MRMT-1 model of breast cancer-induced bone pain to compare the effects of three drugs used clinically morphine, nabilone and zoledronate on tumor progression, bone remodeling and pain relief. We found that chronic morphine reduced the mechanical hypersensitivity induced by the proliferation of the luminal B aggressive breast cancer cells in the tumor-bearing femur and prevented spinal neuronal and astrocyte activation. Using MTT cell viability assay and MRI coupled to FDG PET imaging followed by ex vivo 3D µCT, we further demonstrated that morphine did not directly exert tumor growth promoting or inhibiting effects on MRMT-1 cancer cells but induced detrimental effects on bone healing by disturbing the balance between bone formation and breakdown. In sharp contrast, both the FDA-approved bisphosphonate zoledronate and the synthetic cannabinoid nabilone prescribed as antiemetics to patients receiving chemotherapy were effective in limiting the osteolytic bone destruction, thus preserving the bone architecture. The protective effect of nabilone on bone metabolism was further accompanied by a direct inhibition of tumor growth. As opposed to zoledronate, nabilone was however not able to manage bone tumor-induced pain and reactive gliosis. Altogether, our results revealed that morphine, nabilone and zoledronate exert disparate effects on tumor growth, bone metabolism and pain control. These findings also support the use of nabilone as an adjuvant therapy for bone metastases.
Learn More >Endometriosis, a condition in which uterine tissue grows outside the uterus, is a debilitating disease, affecting millions of women and costing the United States approximately $78 billion annually in pain- related disability. It is also the leading cause of chronic pelvic pain (CPP), which is often unresponsive to existing treatments. Adolescent women with the disease are at particular risk as there are often significant diagnostic delays, which in turn can exacerbate pain. Research and treatment guidelines for adolescents with endometriosis are largely based on studies for adult women due to the limited number of studies focusing on adolescents. The current paper critically reviews the literature as it pertains to endometriosis pathophysiology, mechanisms contributing to CPP, and treatment implications and recommendations with a focus on gaps related to adolescents.
Learn More >It is increasingly recognized that chronic opioid use leads to maladaptive changes in the composition and localization of gut bacteria. Recently, this "opioid-induced dysbiosis" (OID) has been linked to antinociceptive tolerance development in preclinical models and may therefore identify promising targets for new opioid-sparing strategies. Such developments are critical to curb dose escalations in the clinical setting and combat the ongoing opioid epidemic. In this article, we review the existing literature that pertains to OID, including the current evidence regarding its qualitative nature, influence on antinociceptive tolerance, and future prospects. Perspective: This article reviews the current literature on opioid-induced dysbiosis (OID) of gut bacteria, including its qualitative nature, influence on antinociceptive tolerance, and future prospects. This work may help identify targets for new opioid-sparing strategies.
Learn More >Dysfunctional top-down pain modulation is a hallmark of fibromyalgia (FM) and physical exercise is a cornerstone in FM treatment. The aim of this study was to explore the effects of a 15-week intervention of strengthening exercises, twice per week, supervised by a physiotherapist, on exercise-induced hypoalgesia (EIH) and cerebral pain processing in FM patients and healthy controls (HC). FM patients (n = 59) and HC (n = 39) who completed the exercise intervention as part of a multicenter study were examined at baseline and following the intervention. Following the exercise intervention, FM patients reported a reduction of pain intensity, fibromyalgia severity and depression. Reduced EIH was seen in FM patients compared to HC at baseline and no improvement of EIH was seen following the 15-week resistance exercise intervention in either group. Furthermore, a subsample (Stockholm site: FM = 18; HC = 19) was also examined with functional magnetic resonance imaging (fMRI) during subjectively calibrated thumbnail pressure pain stimulations at baseline and following intervention. A significant main effect of exercise (post > pre) was observed both in FM patients and HC, in pain-related brain activation within left dorsolateral prefrontal cortex and caudate, as well as increased functional connectivity between caudate and occipital lobe bordering cerebellum (driven by the FM patients). In conclusion, the results indicate that 15-week resistance exercise affect pain-related processing within the cortico-striatal-occipital networks (involved in motor control and cognition), rather than directly influencing top-down descending pain inhibition. In alignment with this, exercise-induced hypoalgesia remained unaltered.
Learn More >Many patients with chronic pain use prescription opioids. Epigenetic modification of the μ-opioid receptor 1 () gene, which codes for the target protein of opioids, may influence vulnerability to opioid abuse and response to opioid pharmacotherapy, potentially affecting pain outcomes.
Learn More >It is unknown if physiological changes associated with chronic pain could be measured with inexpensive physiological sensors. Recently, acute pain and laboratory-induced pain have been quantified with physiological sensors.
Learn More >Chronic migraine is characterised by persistent headaches for >15 days per month; the intensity of the pain is fluctuating over time. Here, we explored the dynamic interplay of connectivity patterns between regions known to be related to pain processing and their relation to the ongoing dynamic pain experience. We recorded EEG from 80 sessions (20 chronic migraine patients in 4 separate sessions of 25 min). The patients were asked to continuously rate the intensity of their endogenous headache. On different time-windows, a dynamic causal model (DCM) of cross spectral responses was inverted to estimate connectivity strengths. For each patient and session, the evolving dynamics of effective connectivity were related to pain intensities and to pain intensity changes by using a Bayesian linear model. Hierarchical Bayesian modelling was further used to examine which connectivity-pain relations are consistent across sessions and across patients. The results reflect the multi-facetted clinical picture of the disease. Across all sessions, each patient with chronic migraine exhibited a distinct pattern of pain intensity-related cortical connectivity. The diversity of the individual findings are accompanied by inconsistent relations between the connectivity parameters and pain intensity or pain intensity changes at group level. This suggests a rejection of the idea of a common neuronal core problem for chronic migraine.
Learn More >Treatment with baricitinib in combination with topical corticosteroids previously showed greater improvements in itch and sleep versus placebo in adults with moderate-to-severe AD.
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