The journal of pain : official journal of the American Pain Society
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Randomized Controlled Trial
Postoperative subcutaneous instillation of low-dose ketorolac but not hydromorphone reduces wound exudate concentrations of interleukin-6 and interleukin-10 and improves analgesia following cesarean delivery.
The objectives of this study were to test the effects of low-dose ketorolac and hydromorphone added to continuous local anesthetic wound instillation on surgical-site inflammatory mediators, postoperative pain, and opioid consumption. Sixty healthy women undergoing cesarean delivery were enrolled in this randomized, double-blinded study. Patients were randomized to receive a subcutaneous wound instillation of bupivacaine .5% at 10 mg/hour (active control), bupivacaine .5% with ketorolac .6 mg/hour, or bupivacaine .5% with hydromorphone .04 mg/hour for 48 hours postcesarean. Wound exudate was sampled at 4, 24, and 48 hours postcesarean and assayed for interleukins IL-1β, IL-2, IL-6, IL-8, IL-10, and IL-12, tumor necrosis factor (TNF-α), interferon (INF-γ), and granulocyte-macrophage colony stimulating factor (GM-CSF). The addition of ketorolac to bupivacaine significantly decreased IL-6 (P = .012) and IL-10 (P = .005) compared to plain bupivacaine. Ketorolac, but not hydromorphone, was associated with a decrease in pain (P = .018) and analgesic use (P = .020) following cesarean delivery. Our results are compatible with the view that significant analgesics effects are mediated through local modulation of inflammatory events. Low-dose ketorolac administered into surgical wounds exert significant anti-inflammatory and analgesic effects and may be a valuable analgesic alternative to systemic nonsteroidal anti-inflammatories (NSAIDs) but with potentially fewer side effects. ⋯ This article demonstrates that low-dose ketorolac administered into wounds modulates local inflammatory events, decreases postoperative pain, and reduces opioid consumption. These results suggest that administration of NSAIDs into surgical wounds may be an analgesic alternative to higher systemic dosing of NSAIDs.
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Review Meta Analysis
The effects of graded motor imagery and its components on chronic pain: a systematic review and meta-analysis.
Graded motor imagery (GMI) is becoming increasingly used in the treatment of chronic pain conditions. The objective of this systematic review was to synthesize all evidence concerning the effects of GMI and its constituent components on chronic pain. Systematic searches were conducted in 10 electronic databases. All randomized controlled trials (RCTs) of GMI, left/right judgment training, motor imagery, and mirror therapy used as a treatment for chronic pain were included. Methodological quality was assessed using the Cochrane risk of bias tool. Six RCTs met our inclusion criteria, and the methodological quality was generally low. No effect was seen for left/right judgment training, and conflicting results were found for motor imagery used as stand-alone techniques, but positive effects were observed for both mirror therapy and GMI. A meta-analysis of GMI versus usual physiotherapy care favored GMI in reducing pain (2 studies, n = 63; effect size, 1.06 [95% confidence interval, .41, 1.71]; heterogeneity, I(2) = 15%). Our results suggest that GMI and mirror therapy alone may be effective, although this conclusion is based on limited evidence. Further rigorous studies are needed to investigate the effects of GMI and its components on a wider chronic pain population. ⋯ This systematic review synthesizes the evidence for GMI and its constituent components on chronic pain. This review may assist clinicians in making evidence-based decisions on managing patients with chronic pain conditions.
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Randomized Controlled Trial Multicenter Study
A randomized, placebo-controlled study of the impact of the 7-day buprenorphine transdermal system on health-related quality of life in opioid-naïve patients with moderate-to-severe chronic low back pain.
This study evaluated the impact of treatment with Buprenorphine Transdermal System (BTDS) on the health-related quality of life for patients with moderate-to-severe chronic low back pain (CLBP), and the correspondence between quality of life and pain. A multicenter, enriched, double-blind (DB), placebo-controlled, randomized trial evaluated BTDS 10 and 20 μg/hour for treatment of opioid-naïve patients with moderate-to-severe CLBP. The SF-36v2 survey, which measures 8 domains of quality of life, was administered at screening and following an open-label run-in period with BTDS and at weeks 4, 8, and 12 of the DB phase. Post hoc analyses compared SF-36v2 scores between BTDS and placebo groups during the DB phase. Condition burden was examined through comparisons with a U.S. general population sample. Correlations examined the correspondence between quality of life and pain measures. BTDS produced larger improvements than placebo at 12 weeks in all quality-of-life domains (Ps < .05). Treatment group differences in both physical and mental quality of life emerged by 4 weeks. Patients' pretreatment quality of life was worse than that in the general population (Ps < .05); only BTDS treatment eliminated deficits in pain, social functioning, and role limitations due to emotional health. Improvements in quality of life were moderately associated with pain reduction. These data suggest that moderate-to-severe CLBP patients receiving BTDS exhibited better quality of life than patients receiving placebo. ⋯ This post hoc analysis suggests that patients with moderate-to-severe CLBP treated with BTDS exhibit better health-related quality of life than those using placebo within 4 weeks of treatment, and were more likely to exhibit clinically meaningful improvements in quality of life following 12 weeks of treatment.
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Temporal summation (TS) refers to the increased perception of pain with repetitive noxious stimuli. It is a behavioral correlate of wind-up, the spinal facilitation of recurring C-fiber stimulation. In order to utilize TS in clinical pain research, it is important to characterize TS in a wide range of individuals and to establish its test-retest reliability. Building on a fixed-parameter protocol, we developed an individually adjusted protocol to broadly capture thermally generated TS. We then examined the test-retest reliability of TS within-day (intertrial intervals ranging from 2 to 30 minutes) and between-days (intersession interval of 7 days). We generated TS-like effects in 19 of the 21 participants. Strong correlations were observed across all trials over both days (intraclass correlation [ICC] [A, 10] = .97, 95% confidence level [CL] = .94-.99) and across the initial trials between days (ICC [A, 1] = .83, 95% CL = .58-.93). Repeated measures mixed-effects modeling demonstrated no significant within-day variation and only a small (5 out of 100 points) between-day variation. Finally, a Bland-Altman analysis suggested that TS is reliable across the range of observed scores. Without intervention, thermally-generated TS is generally stable within day and between days. ⋯ Our study introduces a new strategy to generate thermal TS in a high proportion of individuals. This study confirms the test-retest reliability of thermal TS, supporting its use as a consistent behavioral correlate of central nociceptive facilitation.
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The C-C motif chemokine ligand 5 (CCL5; also known as regulated on activation, normal T expressed and secreted, or RANTES) is a member of the CC family of chemokines that specifically attract and activate leukocytes to sites of inflammation. Although CCL5 has been implicated in the processing of pain, its detailed mechanisms of action are still unknown. In this study, we investigated the potential of the Met-RANTES, a selective CCL5 receptor antagonist, via peritoneal administration to modulate the recruitment of inflammatory cells in injured sites and attenuate nociceptive responses in a neuropathic pain model in mice. Nociceptive sensitization, immune cell infiltration, multiple cytokine secretion, and opioid peptide expression in damaged nerves were studied. Our results indicated that Met-RANTES-treated mice had less behavioral hypersensitivity after partial sciatic nerve ligation. Macrophage infiltration, pro-inflammatory cytokine (TNFα, IL-1β, IL-6, and IFNγ) protein secretion, and enkephalin, β-endorphin, and dynorphin mRNA expression in damaged nerves following partial sciatic nerve ligation were significantly decreased, and anti-inflammatory cytokine (IL-10) protein was significantly increased in Met-RANTES-treated mice. These results suggest that CCL5 is capable of regulating the microenvironment that controls behavioral hypersensitivity at the level of the peripheral injured site in a murine chronic neuropathic pain model. ⋯ The present study identifies the potent pro-inflammatory potential of CCL5 and verifies the possible role of selective CCL5 receptor inhibitor in a murine neuropathic pain model.