Pain
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Approximately thirty-four percent of people who experience acute low back pain (LBP) will have recurrent episodes. It remains unclear why some people experience recurrences and others do not, but one possible cause is a loss of normal control of the back muscles. We investigated whether the control of the short and long fibres of the deep back muscles was different in people with recurrent unilateral LBP from healthy participants. ⋯ The short fibres were active earlier than long fibres on both sides in the healthy participants (p<0.001) and on the non-painful side in the LBP group (p=0.045), but not on the previously painful side in the LBP group. Activity of deep back muscles is different in people with a recurrent unilateral LBP, despite the resolution of symptoms. Because deep back muscle activity is critical for normal spinal control, the current results provide the first evidence of a candidate mechanism for recurrent episodes.
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Tissue injury initiates a cascade of inflammatory mediators and hyperalgesic substances including prostaglandins, cytokines and chemokines. Using microarray and qRT-PCR gene expression analyses, the present study evaluated changes in gene expression of a cascade of cytokines following acute inflammation and the correlation between the changes in the gene expression level and pain intensity in the oral surgery model of tissue injury and acute pain. Tissue injury resulted in a significant upregulation in the gene expression of interleukin-6 (IL-6; 63.3-fold), IL-8 (8.1-fold), chemokine (C-C motif) ligand 2 (CCL2; 8.9-fold), chemokine (C-X-C motif) ligand 1 (CXCL1; 30.5-fold), chemokine (C-X-C motif) ligand 2 (CXCL2; 26-fold) and annexin A1 (ANXA1; 12-fold). ⋯ However, ketorolac treatment did not have a significant effect on the gene expression of IL-6, IL-8, CCL2, CXCL2 and ANXA1 at the same time point of acute inflammation. These results demonstrate that the upregulation of IL-6, IL-8 and CCL2 gene expression contributes to the development of acute inflammation and inflammatory pain. The lack of effect of ketorolac on the expression of these gene products may be related to the ceiling analgesic effects of non-steroidal anti-inflammatory drugs.
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Intense stress and fear have long been known to give rise to a suppression of pain termed "stress-induced analgesia", mediated by brainstem pain-modulating circuitry, including pain-inhibiting neurons of the rostral ventromedial medulla. However, stress does not invariably suppress pain, and indeed, may exacerbate it. Although there is a growing support for the idea of "stress-induced hyperalgesia", the neurobiological basis for this effect remains almost entirely unknown. ⋯ In addition to the expected increases in body temperature and heart rate, disinhibition of the DMH induced a robust activation of ON-cells, suppression of OFF-cell firing and behavioral hyperalgesia. Blocking ON-cell activation prevented hyperalgesia, but did not interfere with DMH-induced thermogenesis or tachycardia, pointing to differentiation of neural substrates for autonomic and nociceptive modulation within the RVM. These data demonstrate a top-down activation of brainstem pain-facilitating neurons, and suggest a possible neural circuit for stress-induced hyperalgesia.
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Controlled Clinical Trial
Opioid therapy for nonspecific low back pain and the outcome of chronic work loss.
Outcomes of opioid therapy for noncancer pain remain to be more fully explored. Loss of work is among these outcomes. Especially when work loss becomes "chronic" (persists >or=90 days), it has profound psycho-social repercussions that compound suffering of those already in pain. ⋯ Our analysis was not designed to ascertain antecedent causes, or why chronic work loss occurred in the first place. Rather, we focused on an ensuing consequence of opioid therapy, i.e., the outcome of chronic work loss, which occurred far removed in time (>or=90 days) after the worker's recorded date of back injury. The strong associations observed suggest that for most workers opioid therapy did not arrest the cycle of work loss and pain.
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Antihypertensive drugs interact with mediators that are also involved in complex regional pain syndrome (CRPS), such a neuropeptides, adrenergic receptors, and vascular tone modulators. Therefore, we aimed to study the association between the use of antihypertensive drugs and CRPS onset. We conducted a population-based case-control study in the Integrated Primary Care Information (IPCI) database in the Netherlands. ⋯ The association was stronger if ACE inhibitors were used for a longer time period (OR(adjusted): 3.0, 95% CI: 1.1-8.1) and in higher dosages (OR(adjusted): 4.3, 95% CI: 1.4-13.7). None of the other antihypertensive drug classes was significantly associated with CRPS. We conclude that ACE inhibitor use is associated with CRPS onset and hypothesize that ACE inhibitors influence the neuro-inflammatory mechanisms that underlie CRPS by their interaction with the catabolism of substance P and bradykinin.