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More than 300 million patients undergo surgery worldwide each year. Pain associated with these procedures is associated with short- and long-term negative sequelae for patients, healthcare providers, and healthcare systems. The following chapter is a review of the reality of postoperative pain management in everyday clinical routine based on survey- and registry-derived data with a focus on care in adults. Between 30% and up to 80% of patients report moderate to severe pain in the days after surgery. Structures, processes, and outcomes vary widely between hospitals and indicate gaps between evidence-based findings and practice. Pain assessment is not effectively implemented in many hospitals and should consider cultural differences. Few data exist on the situation of pain management in low- and middle-income countries, indicating lack of resources and available medication in many of these areas. Certain types of surgery as well as demographic and clinical factors are associated with increased risk of severe postoperative pain.
Learn More >Diagnostic uncertainty, the perception of a lack of or incorrect label to explain symptoms, has been reported by parents of youth with chronic pain. This study was the first to examine diagnostic uncertainty in both youth with chronic pain and their parents using qualitative methodology. Individual, face-to-face, semi-structured interviews were conducted with twenty youth with chronic pain recruited from a pediatric chronic pain program. Independent interviews were also conducted with one of their parents. Interviews explored participants' memories and perceptions around diagnosis. In-depth thematic analysis revealed four themes: (1) The Function of a Diagnosis. Parents and youth struggled with the meaning of the diagnosis, needed further explanation for the pain, and perceived the 'right' diagnosis (i.e., one that fit with their beliefs) as justification for the pain. (2) Haunted by Something Missing. Negative test results did not provide relief or counter the belief that something serious could have been missed by clinicians. (3) The Search for an Alternative Diagnosis. A search persisted for the 'right' diagnosis, particularly when a non-pharmacological treatment plan was provided. (4) Mistrust in the Medical System. Clinician communication and perceptions of clinicians' uncertainty impacted parent and youth 'buy in' to the diagnosis. Findings suggest that many youth with chronic pain and their parents experience diagnostic uncertainty, which is integrally tied to their past experiences with the medical system. Greater understanding of diagnostic uncertainty may help tailor how clinicians deliver diagnoses to achieve 'buy in', increase understanding of pain and diagnosis, and improve treatment response. Perspective: A major challenge that youth with chronic pain and their parents face is understanding the cause of the pain. Youth with chronic pain and their parents experience uncertainty about their diagnosis, which may be linked to their 'buy in' and treatment response.
Learn More >Although pain reduction after alcohol administration has repeatedly been demonstrated, alcohol effects on advanced and clinically relevant dynamic pain paradigms are still unknown. As such, temporal summation of pain (TSP) and conditioned pain modulation (CPM) indicate mechanisms of endogenous pain modulation and involve certain neurotransmitter systems crucially influenced by alcohol. Our study is the first to investigate acute alcohol effects on TSP and CPM. We investigated 39 healthy subjects in a placebo-controlled within-subject design and targeted alcohol levels of 0.06% (dose 1) and 0.08% (dose 2). Pain threshold, TSP, and CPM were evaluated before and after an alcoholic or placebo drink. Temporal summation of pain was assessed as enhanced pain response to 5 repetitive contact heat stimuli (threshold +3°C). Conditioned pain modulation was tested as pain inhibition when a conditioning stimulus (46°C hot water) was applied concurrently to a test stimulus (contact heat; threshold + 3°C). Both alcohol doses boosted CPM, with a greater effect size for the higher dose. Conditioning stimulus ratings increased after alcohol intake but were not correlated with CPM, suggesting independence of these effects. Temporal summation of pain was not affected by alcohol, and alcohol effects on pain threshold were small and limited to the higher dose. Our findings suggest that analgesic alcohol effects might be mainly driven by an enhancement of endogenous pain inhibition. The frequent use of alcohol as self-medication in chronic pain might be motivated by alcohol temporarily restoring deficient CPM, thus leading to pain relief in the short run and alcohol-related problems in the long run.
Learn More >Prescription opioid misuse is a public health problem that leads to overdose. Although existing interventions focus on limiting prescribing to patients at high risk, individuals may still access prescription opioids dispensed to family members.
Learn More >Migraine is a chronic neurologic disease that can be associated with significant migraine-related impact, disability, and burden. Patient-reported outcome measures (PRO) are included in clinical trials of migraine interventions to capture treatment effects from a patient perspective. Clinical and regulatory guidelines also encourage use of PROs in trials. The Migraine Functional Impact Questionnaire (MFIQ) is a novel PRO measure, assessing the impact of migraine on Physical Function (PF), Usual Activities (UA), Social Function (SF), and Emotional Function (EF), in the past 7 days. Scientific methods recommended to meet the requirements of the U.S. Food and Drug Administration were followed, to ensure that the MFIQ content included outcomes that were relevant to adults with migraine and were clinically relevant, specifically to evaluate preventive treatments for migraine.
Learn More >Mitragyna speciosa (kratom) may hold promise as both an analgesic and treatment for opioid use disorder. Mitragynine, its primary alkaloid constituent, is an opioid receptor ligand. However, the extent to which the in vivo effects of mitragynine are mediated by opioid receptors, or whether mitragynine interacts with other opioid agonists, is not fully established.
Learn More >P2X4 is a ligand-gated ion channel implicated in neuropathic pain. Drug discovery efforts targeting P2X4 have been unsuccessful largely due to the difficulty in engineering specificity and selectivity. Here, we describe for the first time the generation of a panel of diverse monoclonal antibodies (mAbs) to human and mouse P2X4, capable of both positive and negative modulation of channel function. The affinity optimised anti-P2X4 mAb IgG#151-LO showed exquisite selectivity for human P2X4 and induced potent and complete block of P2X4 currents. Site-directed mutagenesis of P2X4 revealed the head domain as a key interaction site for inhibitory mAbs. Inhibition of spinal P2X4 either by intrathecal delivery of an anti-P2X4 mAb, or systemic delivery of an anti-P2X4 bi-specific mAb with enhanced blood-spinal cord barrier permeability, produced long lasting (>7 days) analgesia in a mouse model of neuropathic pain. We therefore propose that inhibitory mAbs binding the head domain of P2X4 have therapeutic potential for the treatment of neuropathic pain.
Learn More >In most mature neurons, low levels of intracellular Cl concentrations ([Cl]) are maintained by channels and transporters, particularly the K-Cl cotransporter 2 (KCC2), which is the only Cl extruder in most neurons. Recent studies have implicated KCC2 expression in the molecular mechanisms underlying neuronal disorders, such as spasticity, epilepsy and neuropathic pain. Alterations in KCC2 expression have been associated with brain-derived neurotrophic factor (BDNF) and its receptor tropomyosin-related kinase B (TrkB). The present review summarizes recent progress regarding the roles of Cl regulators in immature and mature neurons. Moreover, we focus on the role of KCC2 regulation via the BDNF-TrkB pathway in spinal cord injury and rehabilitation, as prior studies have shown that the BDNF-TrkB pathway can affect both the pathological development and functional amelioration of spinal cord injuries. Evidence suggests that rehabilitation using active exercise and mechanical stimulation can attenuate spasticity and neuropathic pain in animal models, likely due to the upregulation of KCC2 expression via the BDNF-TrkB pathway. Moreover, research suggests that such rehabilitation efforts may recover KCC2 expression without the use of exogenous BDNF.
Learn More >To assess the effects of migraine on important life domains and compare differences between respondents with episodic and chronic migraine and between sexes.
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