Pain
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Opioids are essential to the management of pain in many patients, but they also are associated with potential risks for abuse, overdose, and diversion. A number of efforts have been devoted to the development of abuse-deterrent formulations of opioids to reduce these risks. ⋯ Because of the many types of individuals who may be exposed to opioids, an opioid formulation will need to be studied in several populations using various study designs to determine its abuse-deterrent capabilities. It is recommended that the research conducted to evaluate abuse deterrence should include studies assessing: (1) abuse liability, (2) the likelihood that opioid abusers will find methods to circumvent the deterrent properties of the formulation, (3) measures of misuse and abuse in randomized clinical trials involving pain patients with both low risk and high risk of abuse, and (4) postmarketing epidemiological studies.
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Analgesia is particularly susceptible to placebo responses. Recent studies in humans have provided important insights into the neurobiology underlying placebo-induced analgesia. However, human studies provide incomplete mechanistic explanations of placebo analgesia because of limited capacity to use cellular, molecular, and genetic manipulations. ⋯ We found that conditioned (placebo) responding bore 3 of the hallmarks of placebo-induced analgesia: (1) strong interanimal variability in the response, (2) suppression by the opiate antagonist naloxone (5mg/kg subcutaneously), and (3) a positive predictive relationship between the unconditioned analgesic effect and the conditioned (placebo) effect. Because of the operant nature of the assay and the use of only a mild noxious thermal stimulus, we suggest that these results provide evidence of placebo-induced analgesia in a preclinical model that utilizes an affective behavioral end point. This finding may provide opportunities for invasive preclinical studies allowing greater understanding of placebo-induced analgesia, thus paving the way for avenues to harness its benefits.
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Although depressive symptoms are common among those living with back pain, there is limited information on the relationship between postsurgical pain reduction and changes in depressive symptoms. The objective of this prospective cohort study was to examine the change in pain and depressive symptoms and to characterize the relationship between pain and depressive symptoms after lumbar spine surgery. We assessed 260 individuals undergoing lumbar spine surgery preoperatively and postoperatively (3 and 6 months) using a pain intensity numeric rating scale and the Patient Health Questionnaire depression scale. ⋯ However, at 6 months, individuals who experienced a reduction in pain (63%) were nearly twice as likely to experience a reduction in depressive symptoms (odds ratio 1.93, 95% CI 1.15 to 3.25) as those who experienced no change or an increase in pain (31%). We found that most individuals experienced clinically important reductions in pain after surgery. We concluded that those whose pain level was reduced at 6 months were more likely to experience a reduction in depressive symptoms.
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Low back pain is associated with plasticity changes and central hypersensitivity in a subset of patients. We performed a case-control study to explore the discriminative ability of different quantitative sensory tests in distinguishing between 40 cases with chronic low back pain and 300 pain-free controls, and to rank these tests according to the extent of their association with chronic pain. Gender, age, height, weight, body mass index, and psychological measures were recorded as potential confounders. ⋯ As measures of discrimination, we estimated receiver operating characteristics (ROC) and likelihood ratios. Six tests seemed useful (in order of their discriminative ability): (1) pressure pain detection threshold at the site of most severe pain (fitted area under the ROC, 0.87), (2) single electrical stimulation pain detection threshold (0.87), (3) single electrical stimulation reflex threshold (0.83), (4) pressure pain tolerance threshold at the site of most severe pain (0.81), (5) pressure pain detection threshold at suprascapular region (0.80), and (6) temporal summation pain threshold (0.80). Pressure and electrical pain modalities seemed most promising and may be used for diagnosis of pain hypersensitivity and potentially for identifying individuals at risk of developing chronic low back pain over time.
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Neurotrophin-3 (NT-3) is a target-derived neurotrophic factor that regulates sensory neuronal survival and growth. Here we report that NT-3 plays a critical permissive role in cutaneous sensory nerve sprouting that contributes to pain and sensitivity following skin wounding in young animals. ⋯ The requirement for NT-3 for sensory terminal sprouting in vivo is confirmed by the absence of wound-induced hyperinnervation in heterozygous transgenic mice (NT-3(+/-)lacZ). We conclude that upregulation of NT-3 in neonatally wounded skin is a critical factor mediating the sensory nerve sprouting that underlies hypersensitivity and pain following skin injury.