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Background and aims Bariatric surgery remains a mainstay for treatment of morbid obesity. However, long-term adverse outcomes include chronic abdominal pain and persistent opioid use. The aim of this review was to assess the existing data on prevalence, possible mechanisms, risk factors, and outcomes regarding chronic abdominal pain and persistent opioid use after bariatric surgery. Methods PubMed was screened for relevant literature focusing on chronic abdominal pain, persistent opioid use and pharmacokinetic alterations of opioids after bariatric surgery. Relevant papers were cross-referenced to identify publications possibly not located during the ordinary screening. Results Evidence regarding general chronic pain status after bariatric surgery is sparse. However, our literature review revealed that abdominal pain was the most prevalent complication to bariatric surgery, presented in 3-61% of subjects with health care contacts or readmissions 1-5 years after surgery. This could be explained by behavioral, anatomical, and/or functional disorders. Persistent opioid use and doses increased after bariatric surgery, and 4-14% initiated a persistent opioid use 1-7 years after the surgery. Persistent opioid use was associated with severe pain symptoms and was most prevalent among subjects with a lower socioeconomic status. Alteration of absorption and distribution after bariatric surgery may impact opioid effects and increase the risk of adverse events and development of addiction. Changes in absorption have been briefly investigated, but the identified alterations could not be separated from alterations caused solely by excessive weight loss, and medication formulation could influence the findings. Subjects with persistent opioid use after bariatric surgery achieved lower weight loss and less metabolic benefits from the surgery. Thus, remission from comorbidities and cost effectiveness following bariatric surgery may be limited in these subjects. Conclusions Pain, especially chronic abdominal, and persistent opioid use were found to be prevalent after bariatric surgery. Physiological, anatomical, and pharmacokinetic changes are likely to play a role. However, the risk factors for occurrence of chronic abdominal pain and persistent opioid use have only been scarcely examined as have the possible impact of pain and persistent opioid use on clinical outcomes, and health-care costs. This makes it difficult to design targeted preventive interventions, which can identify subjects at risk and prevent persistent opioid use after bariatric surgery. Future studies could imply pharmacokinetic-, pharmacodynamics-, and physiological-based modelling of pain treatment. More attention to social, physiologic, and psychological factors may be warranted in order to identify specific risk profiles of subjects considered for bariatric surgery in order to tailor and optimize current treatment recommendations for this population.
Learn More >Background and aims Health-related quality of life (HRQoL) assessments have been widely used in pain medicine as they are able to reflect the subjective and multidimensional nature of chronic pain. Studies have shown a consistent impairment in HRQoL in different chronic pain conditions. However, it is not known whether HRQoL is impaired in chronic orofacial pain (OFP). The generic 15D HRQoL instrument has been shown to fare as well as or better than other generic HRQoL instruments in the study of chronic pain. The aim was to investigate HRQoL in patients with chronic OFP using the generic 15D HRQoL instrument. The validity of the instrument was tested by studying the association of the 15D data with pain interference. Methods One hundred fifty-one patients (mean age 50 years, SD 15 years, 119 females) were recruited from three tertiary facial pain clinics. HRQoL data of the participants were contrasted with that of an age- and gender- standardized sample of general population by comparing the mean 15D scores and profiles. The data for the general population came from the National Health 2011 Survey representing Finnish population aged 18 years and older. Pain interference was assessed using Brief Pain Inventory. Based on pain interference distribution the participants were divided into tertiles. Statistical comparison between patient and population HRQoL values were performed using Monte-Carlo-type simulations. Statistical significance for the hypothesis of linearity was evaluated by using generalized linear models. Results The mean 15D score of OFP patients (0.824, SD 0.113) was statistically significantly lower than that of the age- and gender-standardized general population (0.929, SD 0.019) (p < 0.001). The difference between the patients and the general population was also clinically important, i.e. over the minimum clinically important difference in the 15D score. All mean 15D dimension values were significantly lower compared with the general population values (p < 0.001 for all dimensions). The largest differences were seen in the dimensions of discomfort and symptoms (0.418, SD 0.222 vs. 0.816, SD 0.027), sleeping (0.693, SD 0.258 vs. 0.838, SD 0.029), and vitality (0.702, SD 0.221 vs. 0.884 SD 0.026). There was a statistically significant linear decrease in the 15D dimension values (p < 0.001) with increasing pain interference. The greatest differences were found on the dimensions of discomfort and symptoms, sleeping and vitality. Conclusions HRQoL is significantly impaired in patients with chronic OFP. A decrease in the 15D dimension values with increasing pain interference indicated convergent validity between 15D and pain interference. Implications The findings suggest that 15D is an appropriate instrument for use in the assessment of HRQoL in OFP patients. By showing the usefulness of the 15D, the present study may encourage further use of generic HRQoL assessments in the study of chronic OFP, and contribute e.g. to the implementation of HRQoL as one of the core outcome measures in future treatment studies on chronic OFP.
Learn More >People with type 2 diabetes (T2D) have a greater prevalence of musculoskeletal and neuropathic pain. This exploratory analysis investigated whether exercise of different intensities leads to changes in self-reported musculoskeletal pain or symptoms of diabetic neuropathy in inactive individuals with type 2 diabetes.
Learn More >to investigate alterations in motor behavior related to pain-related beliefs in persons with peripheral joint conditions.
Learn More >African-American older adults, particularly those who live in economically deprived areas, are less likely to receive pain and psychotropic medications, compared to Whites. This study explored the link between social, behavioral, and health correlates of pain and psychotropic medication use in a sample of economically disadvantaged African-American older adults. This community-based study recruited 740 African-American older adults who were 55+ yeas-old in economically disadvantaged areas of South Los Angeles. Opioid-based and psychotropic medications were the outcome variables. Gender, age, living arrangement, socioeconomic status (educational attainment and financial strain), continuity of medical care, health management organization membership, sleeping disorder/insomnia, arthritis, back pain, pain severity, self-rated health, depressive symptoms, and major chronic conditions were the explanatory variables. Logistic regression was used for data analyses. Arthritis, back pain, severe pain, and poor self-rated health were associated with opioid-based medications. Pain severity and depressive symptoms were correlated with psychotropic medication. Among African-American older adults, arthritis, back pain, poor self-rated health, and severe pain increase the chance of opioid-based and psychotropic medication. Future research should test factors that can reduce inappropriate and appropriate use and prescription of opioid-based and psychotropic medication among economically disadvantaged African-American older adults.
Learn More >Various animal models have been employed to understand the pathogenic mechanism of neuropathic pain. Nitric oxide (NO) is an important molecule in nociceptive transmission and is involved in neuropathic pain. However, its mechanistic actions remain unclear. The aim of this study was to better understand the involvement of neuronal and inducible isoforms of nitric oxide synthase (nNOS and iNOS) in neuropathic pain induced by chronic constriction injury (CCI) of the sciatic nerve in rats. We evaluated pain sensitivity (mechanical withdrawal thresholds using Randall and Selitto, and von Frey tests, and thermal withdrawal thresholds using Hargreaves test) prior to CCI surgery, 14 days post CCI and after intrathecal injections of selective nNOS or iNOS inhibitors. We also evaluated the distribution of NOS isozymes in the spinal cord and dorsal root ganglia (DRG) by immunohistochemistry, synthesis of iNOS and nNOS by Western blot, and NO production using fluorescent probe DAF-2 DA (DA). Our results showed higher number of nNOS and iNOS-positive neurons in the spinal cord and DRG of CCI compared to sham rats, and their reduction in CCI rats after treatment with selective inhibitors compared to non-treated groups. Western blot results also indicated reduced expression of nNOS and iNOS after treatment with selective inhibitors. Furthermore, both inhibitors reduced CCI-evoked mechanical and thermal withdrawal thresholds but only nNOS inhibitor was able to efficiently lower mechanical withdrawal thresholds using von Frey test. In addition, we observed higher NO production in the spinal cord and DRG of injured rats compared to control group. Our study innovatively shows that nNOS may strongly modulate nociceptive transmission in rats with neuropathic pain, while iNOS may partially participate in the development of nociceptive responses. Thus, drugs targeting nNOS for neuropathic pain may represent a potential therapeutic strategy.
Learn More >Chronic pain is associated with poor physical and emotional functioning. Nonpharmacological interventions can help but improvements are small and not sustained. Prior clinical trials do not follow recommendations to comprehensively target objective and performance-based physical function in addition to self-reported physical function.
Learn More >Functional interactions between the mu opioid receptor (MOR) and the metabotropic glutamate receptor 5 (mGluR5) in pain and analgesia have been well established. MMG22 is a bivalent ligand containing MOR agonist (oxymorphamine) and mGluR5 antagonist (MPEP) pharmacophores tethered by a 22-atom linker. MMG22 has been shown to produce potent analgesia in several models of chronic inflammatory and neuropathic pain. This study assessed the efficacy of systemic administration of MMG22 at reducing pain behavior in the spared nerve injury (SNI) model of neuropathic pain in mice, as well as its side effect profile and abuse potential. MMG22 reduced mechanical hyperalgesia and spontaneous ongoing pain after SNI, with greater potency early (10 days) as compared to late (30 days) after injury. Systemic administration of MMG22 did not induce place preference in naïve animals, suggesting absence of abuse liability when compared to traditional opioids. MMG22 also lacked the central locomotor, respiratory, and anxiolytic side effects of its monomeric pharmacophores. Evaluation of mRNA expression showed the transcripts for both receptors were co-localized in cells in the dorsal horn of the lumbar spinal cord and dorsal root ganglia. Thus, MMG22 reduces hyperalgesia after injury in the SNI model of neuropathic pain without the typical centrally mediated side effects associated with traditional opioids.
Learn More >Withdrawal from systemic opioids can induce long-term potentiation (LTP) at spinal C-fibre synapses ("opioid-withdrawal-LTP"). This is considered to be a cellular mechanism underlying opioid withdrawal-induced hyperalgesia, which is a major symptom of the opioid withdrawal syndrome. Opioids can activate glial cells leading to the release of pro-inflammatory mediators. These may influence synaptic plasticity and could thus contribute to opioid-withdrawal-LTP. Here, we report a sexual dimorphism in the mechanisms of morphine-withdrawal-LTP in adult rats.We recorded C-fibre-evoked field potentials in the spinal cord dorsal horn from deeply anaesthetised male and female rats. In both sexes we induced a robust LTP via withdrawal from systemic morphine infusion (8 mg·kg bolus, followed by a one-hour infusion at a rate of 14 mg·kg·h). This paradigm also induced mechanical hypersensitivity of similar magnitude in both sexes. In male rats, systemic but not spinal application of (-)naloxone blocked the induction of morphine-withdrawal-LTP, suggesting the involvement of descending pro-nociceptive pathways. Furthermore, we showed that in male rats, the induction of morphine-withdrawal-LTP required the activation of spinal astrocytes and the release of the pro-inflammatory cytokines tumour necrosis factor (TNF) and interleukin-1 (Il-1). In striking contrast, in female rats, the induction of morphine-withdrawal-LTP was independent of spinal glial cells. Instead, blocking µ-opioid receptors in the spinal cord was sufficient to prevent a facilitation of synaptic strength.Our study revealed fundamental sex differences in the mechanisms underlying morphine-withdrawal-LTP at C-fibre synapses: supraspinal and gliogenic mechanisms in males and a spinal, glial cell-independent mechanism in females.
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