Mechanisms and efficacy of heat and cold therapies for musculoskeletal injury.

Nonpharmacological treatment strategies for acute musculoskeletal injury revolve around pain reduction and promotion of healing in order to facilitate a return to normal function and activity. Heat and cold therapy modalities are often used to facilitate this outcome despite prevalent confusion about which modality (heat vs cold) to use and when to use it. Most recommendations for the use of heat and cold therapy are based on empirical experience, with limited evidence to support the efficacy of specific modalities. This literature review provides information for practitioners on the use of heat and cold therapies based on the mechanisms of action, physiological effects, and the medical evidence to support their clinical use. The physiological effects of cold therapy include reductions in pain, blood flow, edema, inflammation, muscle spasm, and metabolic demand. There is limited evidence from randomized clinical trials (RCTs) supporting the use of cold therapy following acute musculoskeletal injury and delayed-onset muscle soreness (DOMS). The physiological effects of heat therapy include pain relief and increases in blood flow, metabolism, and elasticity of connective tissues. There is limited overall evidence to support the use of topical heat in general; however, RCTs have shown that heat-wrap therapy provides short-term reductions in pain and disability in patients with acute low back pain and provides significantly greater pain relief of DOMS than does cold therapy. There remains an ongoing need for more sufficiently powered high-quality RCTs on the effects of cold and heat therapy on recovery from acute musculoskeletal injury and DOMS.

Continuous low-level heatwrap therapy relieves low back pain and reduces muscle stiffness.

BACKGROUND: Low back pain is a common and costly health care problem. This pilot study evaluated the sensitivity of the 2-stopwatch and Paris plinth methodologies for assessing time-to-onset of pain relief and flexibility, respectively, with continuous, low-level heatwrap therapy. RESEARCH DESIGN AND METHODS: Subjects aged 18 to 55 years with at least moderate baseline acute low back pain were randomly assigned to either heatwrap or oral placebo for 8 hours. Unheated wrap (sham) and oral ibuprofen were included for blinding purposes only. RESULTS: Sixty-one subjects were randomly assigned to either heatwrap (n = 26), oral placebo (n = 25), sham wrap (n = 5), or oral ibuprofen (n = 5). Median time to confirmed first perceptible pain relief and to meaningful pain relief were significantly shorter for the heatwrap group compared with those assigned to oral placebo (96.5 vs > 240.0 min and 215.7 vs > 240.0 min, respectively; P < 0.05 for both). Among subjects receiving the heatwrap, 53.8% reported first perceptible and meaningful relief, compared with 28.0% receiving oral placebo. Subjective measures of pain relief, back stiffness, and global evaluation were more sensitive in detecting treatment differences than the plinth assessments of flexibility, range of motion, and pain. Three adverse events were reported as mild in severity and considered unrelated to study treatment. CONCLUSIONS: The 2-stopwatch methodology is a viable approach for assessing onset of analgesia in low back pain; however, the plinth may not be a reliable method for assessing flexibility. Consistent with published studies involving much larger sample sizes, the heatwrap provided significantly faster and sustained pain relief than oral placebo in subjects with acute low back pain. Clinical Trial Identifier: NCT01045993.

DOV 216,303, a "triple" reuptake inhibitor: safety, tolerability, and pharmacokinetic profile.

This report describes the first evaluation in humans of DOV 216,303, a putative antidepressive that inhibits the reuptake of norepinephrine, serotonin, and dopamine. Subjects received single oral doses of 5 to 150 mg of DOV 216,303 or placebo. At 150 mg, 4 of 7 subjects reported gastrointestinal disturbances. In the multiple-dose phase of the evaluation, subjects received total daily doses of 50, 75, or 100 mg of DOV 216,303 or placebo for 10 days. At a total daily dose of 100 mg, gastrointestinal disturbances were reported in 4 of 6 volunteers. In both the single- and multiple-dose evaluations, no significant changes were noted in vital signs, electrocardiogram, hematology, or clinical chemistry. DOV 216,303 was rapidly absorbed (plasma t(max) of 0.7-1.2 hours and t(1/2) of 3.3-4.4 hours), with dose-proportional C(max) and AUC values. Furthermore, no remarkable difference was apparent in either the C(max) or AUC(tau) of DOV 216,303 following 1 and 10 days of dosing. The present results demonstrate that DOV 216,303 is safe and well tolerated both at single doses of up to 100 mg and multiple doses of up to 100 mg/day for 10 days. Plasma concentrations of DOV 216,303 after doses > 10 mg exceed its reported IC(50) values for inhibition of biogenic amine reuptake.