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Locally Mediated Analgesic Effect of Bradykinin Type 2 Receptor Antagonist HOE 140 During Acute Inflammatory Pain in Rats

George, Jaiben MBBS student; Pulickal, Sachin Jose MBBS student; Singh, Anurag MSc; Gautam, Mayank MSc; Prasoon, Pranav MSc; Kumar, Rahul MSc; Ray, Subrata Basu MD

doi: 10.1097/BCR.0000000000000042
Original Articles

Opioids like morphine form the mainstay of treatment for moderate to severe burn pain. However, lack of dedicated burn care service and potentially serious side effects of opioids often compromise effective treatment. Newer drugs as well as newer routes of administration of analgesic drugs are long-felt needs in the management of burn pain. Bradykinin is a potent inflammatory mediator present at sites of tissue damage. The present study investigated the analgesic effect of bradykinin type 2 receptor antagonist HOE 140 after direct intrawound administration in rats. Also, whether the analgesic effect was locally mediated was further evaluated. Tissue damage was produced by a surgical incision involving skin, fascia, and muscle. It has been reported that there are minor differences in inflammatory mediators underlying incision-related and burn injury–related pain. HOE 140 (1, 3, or 10 μg/10 μl physiological saline) was administered into the wound by a sterile micropipette. After an interval of 30 seconds, the wound was closed. HOE 140-induced analgesic effect was compared to other experimental groups of rats which did not receive any drug or those which were treated with either saline (vehicle) or water. Postincisional pain was determined by monitoring behavior, allodynia, and thermal hyperalgesia. Analgesic effect was also determined after drug administration in contralateral paw. HOE 140 (1, 3, 10 μg) significantly relieved mechanical allodynia and guarding in comparison with vehicle-treated group. The analgesic effect of HOE 140 was locally mediated. Healing of the wound was normal. In conclusion, the results suggest that bradykinin type 2 receptor antagonists such as HOE 140 could be useful in the treatment of acute inflammatory pain.

From the Department of Anatomy, All India Institute of Medical Sciences, New Delhi, India.

Supported by the Department of Biotechnology, Ministry of Science and Technology, Government of India.

Address correspondence to Department of Anatomy, All India Institute of Medical Sciences, New Delhi 110029, India.

© 2014 The American Burn Association