The journal of pain : official journal of the American Pain Society
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Although research on facial expressions of pain has a long history, little is known about the cerebral mechanisms regulating these expressions. It has been suggested that the medial prefrontal cortex (mPFC) might be involved in regulating/inhibiting the degree to which pain is facially displayed. To test whether such a prefrontal regulation does indeed take place, we reduced medial prefrontal excitability via repetitive transcranial magnetic stimulation (rTMS) and assessed its effect on facial expressions. In a within-subject design, facial and subjective responses to experimental pain as well as "situational" pain catastrophizing were assessed in 35 healthy participants; once after receiving low-frequency rTMS over the mPFC (1 Hz) and once after sham stimulation. Compared with sham stimulation, rTMS over the mPFC resulted in enhanced facial expressions of pain, whereas self-report and pain catastrophizing did not change. The current data show that reducing medial prefrontal excitability (via low-frequency rTMS) makes individuals facially more expressive to pain. This finding indicates that the mPFC is crucially involved in the inhibition of facial expressions of pain. Because this effect was independent of changes in self-report and pain catastrophizing suggests that this inhibitory mechanism is mainly governing the facial expression and not the underlying experience of pain. ⋯ Using rTMS, it was shown that the mPFC is causally involved in the downregulation or silencing of one's facial expression of pain. This might explain why individuals with low mPFC functioning (eg, patients with dementia) are facially more expressive in response to pain.
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Diabetes mellitus (DM) has well known costly complications but we hypothesized that costs of care for chronic pain treated with opioid analgesic (OA) medications would also be substantial. In a statewide, privately insured cohort of 29,033 adults aged 18 to 64 years with DM and noncancer pain who filled OA prescription(s) from 2008 to 2012, our outcomes were costs for specific health care services and total costs per 6-month intervals after the first filled OA prescription. Average daily OA dose (4 categories) and total dose (quartiles) in morphine-equivalent milligrams were calculated per 6-month interval after the first OA prescription and combined into a novel OA dose measure. Associations of OA measures with costs of care (n = 126,854 6-month intervals) were examined using generalized estimating equations adjusted for clinical conditions, psychotherapeutic drugs, and DM treatment. Incremental costs for each type of health care service and total cost of care increased progressively with average daily and total OA dose versus no OAs. The combined OA measure identified the highest incremental total costs per 6-month interval that were increased by $8,389 for 50- to 99-mg average daily dose plus >900 mg total dose and, by $9,181 and $9,958 respectively, for ≥100 mg average daily dose plus 301- to 900-mg or >900 mg total dose. In this statewide DM cohort, total health care costs per 6-month interval increased progressively with higher average daily OA dose and with total OA dose but the greatest increases of >$8,000 were distinguished by combinations of higher average daily and total OA doses. ⋯ The higher costs of care for opioid-treated patients appeared for all types of services and likely reflects multiple factors including morbidity from the underlying cause of pain, care and complications related to opioid use, and poorer control of diabetes as found in other studies.
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Theory suggests that as activation of pain concepts in memory increases, so too does subsequent pain perception. Previously, researchers have found that activating pain concepts in memory increases pain perception of subsequent painful stimuli, relative to neutral information. However, they have not attempted to quantify the nature of the association between information studied and ensuing pain perception. We subliminally presented words that had either a low or high degree of association to the word 'pain,' although this was only partially successful and some words were consciously perceived. Participants then received randomized laser heat stimuli, delivered at 1 of 3 intensity levels (low, moderate, high), and we measured the effect of this on behavioral and electrophysiological measures of pain. Participants (N = 27) rated moderate- and high-intensity laser stimuli as more painful after viewing high relative to low associates of pain; these effects remained present when we controlled for measures of mood, anxiety, and physical symptom reporting. Similar effects were observed physiologically, with higher stimulus negativity preceding after high relative to low associates and greater amplitudes for the N2 component of the laser-evoked potential after presentation of high associates in the moderate and high laser intensity conditions. These data support activation-based models of the effects of memory on pain perception. ⋯ Consistent with current theories of memory and pain, we found that high, relative to low activation of pain concepts in memory increased psychological and physiological responses to laser-induced pain. The effect remained regardless of whether participants showed conscious awareness of activation. Theoretical and clinical implications are discussed.
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Neuroplastic changes in brain structure and function are not only a consequence of chronic pain but are involved in the maintenance of pain symptoms. Thus, promotion of adaptive, treatment-responsive neuroplasticity represents a promising clinical target. Emerging evidence about the human brain's response to an array of behavioral and environmental interventions may assist in identifying targets to facilitate increased neurobiological receptivity, promoting healthy neuroplastic changes. Specifically, strategies to maximize neuroplastic responsiveness to chronic pain treatment could enhance treatment gains by optimization of learning and positive central nervous system adaptation. Periods of heightened plasticity have been traditionally identified with the early years of development. More recent research, however, has identified a wide spectrum of methods that can be used to "reopen" and enhance plasticity and learning in adults. In addition to transcranial direct current stimulation and transcranial magnetic stimulation, behavioral and pharmacological interventions have been investigated. Intermittent fasting and glucose administration are two propitious strategies, that are noninvasive, inexpensive to administer, implementable in numerous settings, and might be applicable across differing chronic pain treatments. Key findings and neurophysiological mechanisms are summarized, and evidence for the potential clinical contributions of these two strategies toward ameliorating chronic pain is presented. ⋯ Neuroplastic changes are a defining feature of chronic pain and a complicating factor in treatment. Noninvasive strategies to optimize the brain's response to treatment interventions might improve learning and memory, increase the positive adaptability of the central nervous system, and enhance treatment outcomes.
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Osteoarthritis (OA) pain is most commonly characterized by movement-triggered joint pain. However, in advanced disease, OA pain becomes persistent, ongoing and resistant to treatment with nonsteroidal anti-inflammatory drugs (NSAIDs). The mechanisms underlying ongoing pain in advanced OA are poorly understood. We recently showed that intra-articular (i.a.) injection of monosodium iodoacetate (MIA) into the rat knee joint produces concentration-dependent outcomes. Thus, a low dose of i.a. MIA produces NSAID-sensitive weight asymmetry without evidence of ongoing pain and a high i.a. MIA dose produces weight asymmetry and NSAID-resistant ongoing pain. In the present study, palpation of the ipsilateral hind limb of rats treated 14 days previously with high, but not low, doses of i.a. MIA produced expression of the early oncogene, FOS, in the spinal dorsal horn. Inactivation of descending pain facilitatory pathways using a microinjection of lidocaine within the rostral ventromedial medulla induced conditioned place preference selectively in rats treated with the high dose of MIA. Conditioned place preference to intra-articular lidocaine was blocked by pretreatment with duloxetine (30 mg/kg, intraperitoneally at -30 minutes). These observations are consistent with the likelihood of a neuropathic component of OA that elicits ongoing, NSAID-resistant pain and central sensitization that is mediated, in part, by descending modulatory mechanisms. This model provides a basis for exploration of underlying mechanisms promoting neuropathic components of OA pain and for the identification of mechanisms that might guide drug discovery for treatment of advanced OA pain without the need for joint replacement. ⋯ Difficulty in managing advanced OA pain often results in joint replacement therapy in these patients. Improved understanding of mechanisms driving NSAID-resistant ongoing OA pain might facilitate development of alternatives to joint replacement therapy. Our findings suggest that central sensitization and neuropathic features contribute to NSAID-resistant ongoing OA joint pain.