Enduring prevention and transient reduction of postoperative pain by intrathecal resolvin D1
ABSTRACT Postoperative pain slows surgical recovery, impacting the return of normal function for weeks, months, or longer. Here we report the antihyperalgesic actions of a new compound, resolvin D1 (RvD1), known to reduce inflammation and to suppress pain after peripheral nerve injury, on the acute pain occurring after paw incision and the prolonged pain after skin-muscle retraction. Injection of RvD1 (20-40ng) into the L5-L6 intrathecal space 30minutes before surgery reduces the postincisional primary mechanical hypersensitivity, lowering the peak change by approximately 70% (with 40ng) and reducing the area under the curve (AUC) for the entire 10-day postincisional course by approximately 60%. Intrathecal injection of RvD1 on postoperative day (POD) 1 reduces the hyperalgesia to the same level as that from preoperative injection within a few hours, an effect that persists for the remaining PODs. Tactile allodynia and hyperalgesia following the skin/muscle incision retraction procedure, measured at the maximum values 12 to 14days, is totally prevented by intrathecal RvD1 (40ng) given at POD 2. However, delaying the injection until POD 9 or POD 17 results in RvD1 causing only transient and incomplete reversal of hyperalgesia, lasting for <1day. These findings demonstrate the potent, effective reduction of postoperative pain by intrathecal RvD1 given before or shortly after surgery. The much more limited effect of this compound on retraction-induced pain, when given 1 to 2weeks later, suggests that the receptors or pathways for resolvins are more important in the early than the later stages of postoperative pain. Single intrathecal injections of resolvin D1 in rats before or 1 to 2days after surgery strongly reduce postoperative pain for several weeks.
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ABSTRACT: Mounting of the acute inflammatory response is crucial for host defense and pivotal to the development of chronic inflammation, fibrosis, or abscess formation versus the protective response and the need of the host tissues to return to homeostasis. Within self-limited acute inflammatory exudates, novel families of lipid mediators are identified, named resolvins (Rv), protectins, and maresins, which actively stimulate cardinal signs of resolution, namely, cessation of leukocytic infiltration, counterregulation of proinflammatory mediators, and the uptake of apoptotic neutrophils and cellular debris. The biosynthesis of these resolution-phase mediators in sensu stricto is initiated during lipid-mediator class switching, in which the classic initiators of acute inflammation, prostaglandins and leukotrienes (LTs), switch to produce specialized proresolving mediators (SPMs). In this work, we review recent evidence on the structure and functional roles of these novel lipid mediators of resolution. Together, these show that leukocyte trafficking and temporal spatial signals govern the resolution of self-limited inflammation and stimulate homeostasis.Cold Spring Harbor perspectives in biology 10/2014; 7(2). DOI:10.1101/cshperspect.a016311 · 8.23 Impact Factor
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ABSTRACT: Arthritis-associated inflammatory pain represents a serious medical problem worldwide. Current treatments for arthritic pain are not very effective and cause unwanted side effects. Resolvins, including the resolvin D and resolvin E series, are a family of novel endogenous lipid mediators derived from ω-3 polyunsaturated fatty acids and display potent anti-inflammatory and pro-resolution actions in animal models of inflammation. Emerging evidence also points to a potent anti-hyperalgesic role of resolvins in animal models of inflammatory pain. The study by Lima-Garcia et al. in this issue of the BJP demonstrated that systemic treatment with 17(R)-hydroxy-docosahexaenoic acid (17(R)HDoHE), the precursor of resolvin D series and its product, aspirin-triggered resolvin D1 (AT-RvD1), at very low doses (1 µg·kg(-1)), reduced inflammatory pain in an adjuvant-induced arthritis model. Particularly 17(R)HDoHE reduced joint stiffness but not paw and joint oedema. Given their potency and safety profile, resolvins may represent a new class of analgesics well suited to treating inflammatory pain associated with arthritis. LINKED ARTICLE This article is a commentary on Lima-Garcia et al., pp. 278-293 of this issue. To view this paper visit http://dx.doi.org/10.1111/j.1476-5381.2011.01345.x.British Journal of Pharmacology 03/2011; 164(2):274-7. DOI:10.1111/j.1476-5381.2011.01348.x · 4.99 Impact Factor
- European Psychiatry 01/2011; 26:1580-1580. DOI:10.1016/S0924-9338(11)73284-9 · 3.21 Impact Factor