The journal of pain : official journal of the American Pain Society
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Multiple investigators have recently asked whether neuroimaging has shown that chronic pain is a brain disease. We review the clinical implications of seeing chronic pain as a brain disease. Abnormalities noted on imaging of peripheral structures have previously misled the clinical care of patients with chronic pain. We also cannot assume that the changes associated with chronic pain on neuroimaging are causal. When considering the significance of neuroimaging results, it is important to remember that "disease" is a concept that arises out of clinical medicine, not laboratory science. Following Canguilhem, we believe that disease is best defined as a structural or functional change that causes disvalue to the whole organism. It is important to be cautious in our assertions about chronic pain as a brain disease because these may have negative effects on 1) the therapeutic dialogue between clinicians and patients; 2) the social dialogue about reimbursement for pain treatments and disability due to pain; and 3) the chronic pain research agenda. Considered scientifically, we may be looking for the cause of chronic pain through neuroimaging, but considered clinically, we are in fact often looking to validate pain complaints. We should not yield to the temptation to validate pain with the magnetic resonance imaging scanner (structural or functional). We should not see pain as caused by the brain alone. Pain is not felt by the brain, but by the person. ⋯ Neuroimaging investigators have argued that brain imaging may demonstrate that chronic pain is a brain disease. We argue that "disease" is a clinical concept and that conceiving of chronic pain as a brain disease can have negative consequences for research and clinical care of patients with chronic pain.
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There is a well-established comorbidity between migraine and anxiety and depression (A/D). Here, we investigate whether this relationship is specific for migraine and A/D or whether other types of pain are also consistently associated with A/D. In addition, we test whether there is a consistent association between migraine and other types of pain when comorbidity with A/D is controlled for. Data on A/D, migraine, and 6 nonheadache pain locations (back, neck, orofacial area, abdomen, joints, and chest) were analyzed in 2,981 participants from the Netherlands Study of Depression and Anxiety (NESDA). It was tested whether the prevalence of pain in each individual location, as well as the total number of pain locations, depended on A/D and migraine status. A/D was consistently associated with pain in all measured locations. Migraine was also associated with pain in all anatomical sites, but these associations weakened substantially after correction for A/D severity, suggesting that a considerable part of the comorbidity of migraine and other types of pain may be explained by A/D. These findings emphasize the importance of accounting for A/D in studies of pain comorbidity. This will contribute to a better understanding of the mechanisms underlying A/D and pain. ⋯ Anxiety and depression are consistently associated with pain, regardless of anatomical site. These disorders may be important factors in the co-occurrence of different pain disorders. Awareness of this comorbidity and a better understanding of the underlying mechanisms may facilitate adequate treatment of both types of conditions.
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Oxycodone hydrochloride controlled-release, also known as extended-release oxycodone (ER oxycodone), was reformulated with physicochemical barriers to crushing and dissolving intended to reduce abuse through nonoral routes of administration (ROAs) that require tampering (eg, injecting and snorting). Manufacturer shipments of original ER oxycodone (OC) stopped on August 5, 2010, and reformulated ER oxycodone (ORF) shipments started August 9, 2010. A sentinel surveillance sample of 140,496 individuals assessed for substance abuse treatment at 357 U.S. centers between June 1, 2009, and March 31, 2012, was examined for prevalence and prescription-adjusted prevalence rates of past-30-day abuse via any route, as well as abuse through oral, nonoral, and specific ROAs for ER oxycodone and comparators (ER morphine and ER oxymorphone) before and after ORF introduction. Significant reductions occurred for 8 outcome measures of ORF versus OC historically. Abuse of ORF was 41% lower (95% CI: -44 to -37) than historical abuse for OC, with oral abuse 17% lower (95% CI: -23 to -10) and nonoral abuse 66% lower (95% CI: -69 to -63). Significant reductions were not observed for comparators. Observations were consistent with the goals of a tamper resistant formulation for an opioid. Further research is needed to determine the persistence and generalizability of these findings. ⋯ This article presents preliminary findings indicating that 8 outcome measures of abuse of a reformulated ER oxycodone were lower than that for original ER oxycodone historically, particularly through nonoral ROAs that require tampering (ie, injection, snorting, smoking), in a sentinel sample of individuals assessed for substance use problems for treatment planning.
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Fresh empirical evidence supports the notion that fear of movement-related pain can be acquired through associative learning. In the context of these findings, 2 ideas are appealing, yet uninvestigated. The first is that merely the intention to perform a painful movement acts as a covert conditioned stimulus (CS) inducing defensive fear responses (ie, gaining excitatory properties following Pavlovian acquisition). The second idea is that after extinction, fear of movement-related pain can easily be reinstated after unexpected painful stimuli (ie, reinstatement). In a voluntary differential conditioning movement paradigm with movements as CSs and a painful electrocutaneous stimulus as the unconditioned stimulus (pain-US), 2 groups were included (Experimental/Control). One movement (CS+) was followed by the pain-US and another movement (CS-) was not during acquisition, while the CS+ was no longer reinforced during extinction. Next, the Experimental group received 2 reinstating pain-USs, whereas the Control group did not. The CS+ but not the CS- evoked fear of movement-related pain in self-reports and eye-blink startles. Intriguingly, the mere intention to perform the painful movement produced higher eye-blink startle responses than the intention to perform the nonpainful movement. We also demonstrated nondifferential reinstatement in the verbal fear ratings in the Experimental group only. ⋯ This study demonstrates that the mere intention to perform a painful movement prior to the actual painful movement itself can come to elicit conditioned fear responses. These results suggest that actual movement may not be necessary to elicit pain-related fear responses, maintaining chronic pain-related fear, avoidance, and disability.
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Morphine is among the most prevalent analgesics prescribed for chronic pain. However, prolonged morphine treatment results in the development of analgesic tolerance. An abundance of evidence has accumulated indicating that central nervous system glial cell activity facilitates pain transmission and opposes morphine analgesia. While the midbrain ventrolateral periaqueductal gray (vlPAG) is an important neural substrate mediating pain modulation and the development of morphine tolerance, no studies have directly assessed the role of PAG glia. Here we test the hypothesis that morphine-induced increases in vlPAG glial cell activity contribute to the development of morphine tolerance. As morphine is primarily consumed for the alleviation of severe pain, the influence of persistent inflammatory pain was also assessed. Administration of morphine, in the absence of persistent inflammatory pain, resulted in the rapid development of morphine tolerance and was accompanied by a significant increase in vlPAG glial activation. In contrast, persistent inflammatory hyperalgesia, induced by intraplantar administration of complete Freund's adjuvant (CFA), significantly attenuated the development of morphine tolerance. No significant differences were noted in vlPAG glial cell activation for CFA-treated animals versus controls. These results indicate that vlPAG glia are modulated by a persistent pain state, and implicate vlPAG glial cells as possible regulators of morphine tolerance. ⋯ The development of morphine tolerance represents a significant impediment to its use in the management of chronic pain. We report that morphine tolerance is accompanied by increased glial cell activation within the vlPAG, and that the presence of a persistent pain state prevented vlPAG glial activation and attenuated morphine tolerance.