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To evaluate secondary outcomes including changes in functioning and disability associated with galcanezumab, a humanized monoclonal antibody to calcitonin gene-related peptide, in patients with chronic migraine.
Learn More >Chronic headache pain is one of the most commonly reported comorbid pain conditions with post-traumatic stress disorder (PTSD) patients and resistant to effective treatment, yet no combined preclinical model of the two disorders has been reported. Here, we used a modified chronic headache pain model to investigate the contribution of single prolonged stress (SPS) model of PTSD with sodium nitroprusside (SNP)-induced hyperalgesia. Injection of SNP (2 mg/kg, i.p.) occurred every other day from day 7 to day 15 after initiation of SPS in rats. Paw withdrawal threshold (PWT) to von Frey stimuli and tail flick latencies (TFL) dramatically decreased as early as 7 days after SPS and lasted until at least day 21. Basal PWT and TFL also significantly decreased during the SNP treatment period. The lower nociceptive thresholds recovered in 6 days following the final SNP injection in SNP group, but not in SPS + SNP group. Elevated nociceptin/OFQ (N/OFQ) levels observed in cerebrospinal fluid of SPS rats were even higher in SPS + SNP group. Glial fibrillary acidic protein (GFAP) and N/OFQ peptide (NOP) receptor mRNA expression increased in dorsal root ganglia (DRG) 21 days after SPS exposure; mRNA increases in the SPS/SNP group was more pronounced than SPS or SNP alone. GFAP protein expression was upregulated in trigeminal ganglia by SPS. Our results indicate that traumatic stress exaggerated chronic SNP-induced nociceptive hypersensitivity, and that N/OFQ and activated satellite glia cells may play an important role in the interaction between both conditions.
Learn More >Pain sensation is powerfully modulated by signal processing in the brain, and pain becomes chronic with the dysfunction of the pain modulatory system; however, the underlying mechanisms are unclear. We found that the metabotropic glutamate receptor 5 (mGluR5) in the periaqueductal gray (PAG), the key area of endogenous pain modulation, is persistently active in normal conditions to maintain an appropriate sensory perception. In the neuropathic pain condition, Homer1a, an activity-dependent immediate early gene product, disrupted the persistent mGluR5 activity resulting in chronic pain. Remarkably a single-time blockage of the mGluR5 resulted in chronic neuropathic pain-like symptoms even in the absence of nerve injury. The decline of mGluR5 activity induced the pain modulatory dysfunction with a profound reduction of excitability of PAG neurons. These findings uncover the role of the persistent mGluR5 activity in vivo and provide new insight into how pain becomes chronic with the maladaptive coping of the PAG to pain sensation.
Learn More >Clinical tools assessing tactile acuity in people with persistent pain have limitations. Therefore, a novel and semi-automated tool was developed: The Imprint Tactile Acuity Device (iTAD).
Learn More >Neuropathic cancer pain (NcP) is associated with worse treatment responses and specific therapy indications, but a standardized clinical diagnosis of NcP is still lacking.This is a prospective observational study on cancer outpatients, comparing different clinical approaches to NcP evaluation. A three-step assessment of NcP was performed using DN4 (cut-off of 4), palliative care physician Clinical Impression, including etiology and pain syndrome identification, and Retrospective Clinical Classification by a board of specialists with the IASP Neuropathic Pain Special Interest Group criteria. NcP classification was specifically referred to pain directly due to cancer.350 patients were assessed, NcP prevalence was 20%, 95%CI [15.9% – 24.6%], 36,9%, (95% CI 31.6% – 42.1%) and 28.6%, (95%CI 23.8% – 33.9%) according respectively to DN4, Clinical Impression and Retrospective Clinical Classification. Cohen's Kappa concordance coefficient between DN4 and Retrospective Clinical Classification was 0.57, 95%CI [0.47 – 0.67], indicating moderate concordance. Higher percentages of discordance were found for specific pain syndromes like pain due to deep soft tissue infiltration and pain associated with tenesmus. Disagreement among clinicians accounted also for different NcP diagnoses and highlighted lack of homogeneous clinical criteria. Rigorous application of etiological and syndrome diagnosis to explain pain cause, associated with standardized diagnostic criteria and assessment of pain characteristics, that is also specific of the cancer pain condition could improve clinical classification of NcP.
Learn More >Approximately one-half of patients with substance use disorders (SUD) experience chronic pain. Yet how patients perceive the relationship between their substance use and chronic pain remains poorly understood. We sought to identify how patients with comorbid SUD and chronic pain describe the relationship between, and mechanisms linking, these conditions. We conducted qualitative interviews with 34 patients engaged in SUD treatment who were also diagnosed with chronic pain. Interviews were transcribed verbatim and coded by both primary and secondary coders. Qualitative content analysis guided coding and analysis. Patient interviews revealed three primary pathways. One group of participants described SUD as developing independently from their experiences of chronic pain. A second group of participants described turning to substances to self-manage or cope with the physical and emotional aspects of chronic pain. A third group of participants described encounters with opioid medications as the causal agent initiating a SUD. Our findings build upon research that has identified chronic pain and SUD as developmentally similar and mutually reinforcing, by revealing the ways in which patients themselves understand and experience the interconnections between their substance use and chronic pain.
Learn More >While clinical studies support the suggestion that stress is a risk factor for painful chemotherapy-induced peripheral neuropathy (CIPN), there is little scientific validation to support this link. Here, we evaluated the impact of stress on CIPN induced by oxaliplatin, and its underlying mechanisms, in male and female rats. A single dose of oxaliplatin produced mechanical hyperalgesia of similar magnitude in both sexes, still present at similar magnitude in both sexes, on day 28. Adrenalectomy mitigated oxaliplatin-induced hyperalgesia, in both sexes. To confirm the role of neuroendocrine stress axes in CIPN, intrathecal administration of antisense oligodeoxynucleotide (AS-ODN) targeting β2-adrenergic receptor mRNA both prevented and reversed oxaliplatin-induced hyperalgesia, only in males. In contrast, glucocorticoid receptor AS-ODN, prevented and reversed oxaliplatin-induced hyperalgesia in both sexes. Unpredictable sound stress enhanced CIPN, in both sexes. The administration of stress hormones, epinephrine, corticosterone and their combination, at stress levels, mimicked the effects of sound stress on CIPN, in males. In females, only corticosterone mimicked the effect of sound stress. Also a risk factor for CIPN, early life stress, was evaluated by producing both stress-sensitive (produced by neonatal limited bedding, NLB) and stress-resilient (produced by neonatal handling, NH) phenotypes in adults. While NLB significantly enhanced CIPN only in female adults, NH significantly attenuated CIPN, in both sexes. Our study demonstrates a sexually dimorphic role of the two major neuroendocrine stress axes in oxaliplatin-induced neuropathic pain.
Learn More >Bone cancer pain (BCP) remains a difficult clinical problem. This study examined whether pioglitazone, a peroxisome proliferator-activated receptor gamma (PPARγ) agonist, is effective for attenuating BCP, and investigated the interaction between activation of PPARγ and phosphatase and tensin homolog deleted from chromosome 10 (PTEN) / mammalian target of rapamycin (mTOR) signal in the spinal dorsal horn (SDH) of BCP rats.
Learn More >Chronic pruritus has considerable implications for quality of life (QoL). However, its impact on health-related QoL and economic burden is not fully characterized. We administered a cross-sectional survey of 132 patients with chronic pruritus using the Health Utilities Index Mark 3 (HUI3) instrument. Normative data from healthy adults (n=4,187) were obtained from the Joint Canada/U.S. Survey of Health. Quality-adjusted life-year (QALY) loss and economic costs were estimated based on HUI3 scores of chronic pruritus patients vs. controls. Patients with chronic pruritus had lower overall health performance compared to the control (0.56±0.03 vs. 0.86±0.003, p<0.001). In multivariable regression, chronic pruritus was associated with worse overall health performance (coefficient -0.30, 95% CI [-0.33 to -0.27]), most accentuated in the domains of pain (coefficient -0.24, [-0.28 to -0.21]) and emotion (coefficient -0.11, [-0.13 to -0.10]). The reduced HUI3 score correlated to 5.5 average lifetime QALYs lost per patient. Using conservative estimates for willingness-to-pay, the QALY loss translated to an individual lifetime economic burden of $274,921 and a societal burden of $88.8 billion. Chronic pruritus is associated with significant QoL impairment. The economic burden of chronic pruritus highlights the necessity of further research into management options.
Learn More >Spinal cord stimulation (SCS) is an important treatment modality used to treat chronic neuropathic pain. However, reported success rates of 26%-70% entail an increased focus on patient selection. An area of core interest is psychological evaluation, often using scales such as the Pain Catastrophizing Scale (PCS). The aim of this study was to assess the relation between baseline PCS scores obtained before implantation and SCS outcomes defined as (1) Rating on Patients' Global Impression of Change scale (PGIC), (2) Pain relief on the Numeric Rating Scale (NRS), (3) Cessation of pain medication, and (4) Risk of permanent explantation.
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