curcumin and Nociceptive-Pain

Managing burn injury-associated pain and wounds is a major unresolved clinical problem. Opioids, nonsteroidal antiinflammatory drugs (NSAIDs), antidepressants and anticonvulsants remain the most common forms of analgesic therapy to treat burn patients. However, prolonged treatment with these drugs leads to dose escalation and serious side effects. Additionally, severe burn wounds cause scarring and are susceptible to infection. Recent encouraging findings demonstrate that curcumin, a major bioactive component found in turmeric, is a natural pharmacotherapeutic for controlling both severe burn pain and for improved wound healing.. This article covers current pr-clinical and clinical studies on the analgesic and wound healing effects. Particular emphasis has been placed on studies aimed at developing improved curcumin delivery vehicles that increase its bioavailability. Based on the available evidence, a hypothesis is proposed that the dual beneficial effects of curcumin, analgesia and enhanced wound healing are mediated through common anti-inflammatory mechanisms.. Emerging studies have demonstrated that curcumin is a promising investigational drug to treat both pain and wounds. The adequate control of severe burn pain, particularly over the long courses required for healing, as well improvements in burn wound healing are unmet clinical needs.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Burns; Clinical Trials as Topic; Curcumin; Drug Delivery Systems; Drug Evaluation, Preclinical; Nociceptive Pain; Wound Healing

"Curcumae Radix", the dried rhizomes of Curcuma kwangsiensis documented in Chinese pharmacopoeia, has been traditionally used for the treatment of inflammatory and pain diseases, such as jaundice and red urine, cleaning the heart-fire and depression, arthralgia, and dysmenorrhea. However, according to literature surveys, anti-inflammatory and antinociceptive studies of C. kwangsiensis have been seldom reported so far.. The current study focuses on the anti-inflammatory and antinociceptive effects of C. kwangsiensis and discovering the bioactive compounds for its traditional usages both in vivo and in vitro, which could provide scientific justification about its traditional use.. The anti-inflammatory and antinociceptive assays of various layers (ME, EA, AQS) from C. kwangsiensis were achieved by carrageenan-induced paw edema and acetic acid-induced writhing animal models, respectively. The most bioactive part, EA layer was further phytochemically investigated by multiple step chromatography techniques. The structures of these isolates were unambiguously elucidated by means of extensive spectroscopic and chemical methods, and comparison with corresponding data of the reported literature. Four major sesquiterpenoids (4, 6, 14, and 15) were achieved for their anti-inflammatory and antinociceptive assays by the two aforementioned animal models in vivo. All the isolated compounds were evaluated for their anti-inflammatory effects via detecting inflammatory mediator releases (COX-2, IL-1β, and TNF-α) in RAW 264.7 macrophage cells induced by LPS.. The ME and EA layers significantly alleviated the paw edema caused by carrageenan and decreased the number of writhes induced by acetic acid at the dose of 200 and/or 100 mg/kg in comparison to the control group (p < 0.01/0.05), and the EA layer exhibited better activity than that of ME layer. Subsequent phytochemical investigation on EA layer of C. kwangsiensis exhibited that three new terpenoid compounds (1-3), identified as (12Z,14R)-7β-hydroxylabda-8(17),12-diene-14,15,16-triol (1), (12Z,14S)- 7β-hydroxlabda-8(17),12-diene-14,15,16-triol (2), and (4S)-hydroxy-(8)-methoxy-(5S)-(H)-guaia1(10),7(11)-dien-12,8-olide (3), together with twenty-two known analogs were isolated. Furthermore, four major sesquiterpenoids (4, 6, 14, and 15) significantly relieved the paw edema and number of writhes at 100 and/or 50 mg/kg (p < 0.05/0.01). Likewise, the majority of sesqui- and diterpenoids isolated could remarkably inhibited the secretion of inflammatory mediators (COX-2, IL-1β, and TNF-α) in LPS-stimulated RAW 264.7 macrophages cells at the concentration of 20 μg/mL, comparable to DXM used as the positive control. All the results suggested that EA layer from C. kwangsiensis possessed the anti-inflammatory and antinociceptive activities, and these sesqui- and diterpenoids could be the effective constituents responsible for relieving inflammation.. The present studies undoubtedly determined the anti-inflammatory and antinociceptive material basis of C. kwangsiensis, including the EA layer and its precise components, which presented equivalent or better anti-inflammatory effects than that of positive control (ASP/DXM) in vivo and in vitro. These results not only would account for scientific knowledge for traditional use of C. kwangsiensis, but also provide credible theoretical foundation for the further development of anti-inflammatory and antinociceptive agents.

Topics: Analgesics; Animals; Anti-Inflammatory Agents; Behavior, Animal; Curcuma; Disease Models, Animal; Inflammation; Inflammation Mediators; Macrophages; Male; Mice; Mice, Inbred ICR; Nociceptive Pain; Pain Perception; Pain Threshold; Plant Extracts; RAW 264.7 Cells; Terpenes

Cisplatin is commonly used against several solid tumors, and oxaliplatin is an effective cytotoxic drug used in colorectal cancer. A major clinical issue affecting 10-40 % of patients treated with cisplatin or oxaliplatin is severe peripheral neuropathy causing sensory, motor, and autonomic dysfunction, with symptoms including cold sensitivity and neuropathic pain. The biochemical basis of the neurotoxicity is uncertain, but is associated with oxidative stress. Curcumin (a natural phenolic yellow pigment) has strong antioxidant, anticancer, and anti-inflammatory actions. Here we report the possible protective effect of curcumin on some cisplatin- and oxaliplatin-induced behavioral, biochemical, and histopathological alterations in rats. Twenty-four hours after the end of treatments some motor and behavioral tests (motor activity, thermal and mechanical nociception, and neuromuscular coordination) were conducted, followed by measuring plasma neurotensin platinum concentration in the sciatic nerve, and studying the histopathology of the sciatic nerve. Oxaliplatin (4 mg/kg) and cisplatin (2 mg/kg) [each given twice weekly, in a total of nine intraperitoneal injections over 4.5 weeks] significantly increased plasma neurotensin concentration, caused specific damage in the histology of the sciatic nerve and produced variable effects in the motor and behavioral tests. Oral curcumin (10 mg/kg, 4 days before the platinum drug, and thereafter, concomitantly with it for 4.5 weeks) reversed the alterations in the plasma neurotensin and sciatic nerve platinum concentrations, and markedly improved sciatic nerve histology in the platinum-treated rats. Larger experiments using a wider dose range of oxaliplatin, cisplatin, and curcumin are required to fully elucidate the possible protective role of curcumin in platinum-induced neurotoxicity.

Topics: Administration, Oral; Animals; Anti-Inflammatory Agents, Non-Steroidal; Antineoplastic Agents; Behavior, Animal; Cisplatin; Curcumin; Disease Models, Animal; Male; Motor Activity; Nervous System Diseases; Neurotensin; Nociceptive Pain; Organoplatinum Compounds; Oxaliplatin; Peripheral Nervous System; Rats; Rats, Wistar; Sciatic Nerve