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      Characterization of Nociceptive Behaviors Induced by Formalin in the Glabrous and Hairy Skin of Rats

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          Abstract

          Introduction:

          Glabrous skin and hairy skin are innervated by different types of noxious fibers. However, the different nociceptive behaviors induced by formalin, a commonly used model of acute inflammatory pain, have not yet been systematically examined in the glabrous and hairy skin.

          Methods:

          In this study, we compared nociceptive behaviors induced by formalin injections (2%, 4%, and 8%) into either glabrous skin (plantar surface) of the hind paw or hairy skin of the hind limb in adult rats.

          Results:

          A typical biphasic nociceptive response was seen after formalin injection into the plantar surface of the hind paw. A brief interphase separates the first and second phases where nociceptive behaviors were barely spotted. However, following subcutaneous injection into the hairy skin nociceptive behaviors were only seen after 10 minutes of formalin injection, which correlates in time with the second phase of the formalin response. First phase nociceptive behaviors were never seen with hairy skin injection, even following multiple injections of formalin.

          Conclusion:

          These data suggest that nociceptive behaviors and spinal responses induced by formalin injections to glabrous and hairy skin areas are different, and that the first and second phases may be mediated through different noxious afferent fibers.

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          Most cited references29

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          The formalin test in mice: dissociation between inflammatory and non-inflammatory pain.

          The formalin test in mice is a valid and reliable model of nociception and is sensitive for various classes of analgesic drugs. The noxious stimulus is an injection of dilute formalin (1% in saline) under the skin of the dorsal surface of the right hindpaw. The response is the amount of time the animals spend licking the injected paw. Two distinct periods of high licking activity can be identified, an early phase lasting the first 5 min and a late phase lasting from 20 to 30 min after the injection of formalin. In order to elucidate the involvement of inflammatory processes in the two phases, we tested different classes of drugs in the two phases independently. Morphine, codeine, nefopam, and orphenadrine, as examples of centrally acting analgesics, were antinociceptive in both phases. In contrast, the non-steroid anti-inflammatory drugs indomethacin and naproxen and the steroids dexamethasone and hydrocortisone inhibited only the late phase, while acetylsalicylic acid (ASA) and paracetamol were antinociceptive in both phases. The results demonstrate that the two phases in the formalin test may have different nociceptive mechanisms. It is suggested that the early phase is due to a direct effect on nociceptors and that prostaglandins do not play an important role during this phase. The late phase seems to be an inflammatory response with inflammatory pain that can be inhibited by anti-inflammatory drugs. ASA and paracetamol seem to have actions independent of their inhibition of prostaglandin synthesis and they also have effects on non-inflammatory pain.
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            The formalin test: A quantitative study of the analgesic effects of morphine, meperidine, and brain stem stimulation in rats and cats

            A method for assessing pain and analgesia in rats and cats is described. The procedure involves subcutaneous injection of dilute formalin into the forepaw, after which the animal's responses are rated according to objective behavioral criteria. The formalin test is a statistically valid technique which has two advantages over other pain tests: (1) little or no restraint is necessary, permitting unhindered observation of the complete range of behavioral responses; and (2) the pain stimulus is continuous rather than transient, thus bearing greater resemblance to most clinical pain. The analgesic effects of morphine, meperidine, and stimulation of the periaqueductal grey matter are evaluated using this test.
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              Evidence for a central component of post-injury pain hypersensitivity.

              C J Woolf (2015)
              Noxious skin stimuli which are sufficiently intense to produce tissue injury, characteristically generate prolonged post-stimulus sensory disturbances that include continuing pain, an increased sensitivity to noxious stimuli and pain following innocuous stimuli. This could result from either a reduction in the thresholds of skin nociceptors (sensitization) or an increase in the excitability of the central nervous system so that normal inputs now evoke exaggerated responses. Because sensitization of peripheral receptors occurs following injury, a peripheral mechanism is widely held to be responsible for post-injury hypersensitivity. To investigate this I have now developed an animal model where changes occur in the threshold and responsiveness of the flexor reflex following peripheral injury that are analogous to the sensory changes found in man. Electrophysiological analysis of the injury-induced increase in excitability of the flexion reflex shows that it in part arises from changes in the activity of the spinal cord. The long-term consequences of noxious stimuli result, therefore, from central as well as from peripheral changes.
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                Author and article information

                Journal
                Basic Clin Neurosci
                Basic Clin Neurosci
                BCN
                BCN
                Basic and Clinical Neuroscience
                Iranian Neuroscience Society
                2008-126X
                2228-7442
                January 2017
                : 8
                : 1
                : 37-42
                Affiliations
                [1. ]Department of Nursing, Faculty of Nursing and Midwifery, Torbat Heydariyeh University of Medical Sciences, Torbat Heydariyeh, Iran.
                [2. ]Department of Medical Basic Sciences and Neuroscience Research Center, Torbat Heydariyeh University of Medical Sciences, Torbat Heydariyeh, Iran.
                [3. ]Department of Information Physiology, National Institute for Physiological Sciences, Okazaki, Japan.
                [4. ]School of Life Science, University for Advanced studies (SOKENDAI), Okazaki, Japan.
                Author notes
                [* ]Corresponding Author: Hassan Azhdari-Zarmehri, PhD, Address: Department of Medical Basic Sciences and Neuroscience Research Center, Torbat Heydariyeh University of Medical Sciences, Torbat Heydariyeh, Iran., Tel:+98 (515) 2224397, E-mail: azhdarih1@ 123456thums.ac.ir
                [* ]Co-Corresponding Author: Hidemasa Furue, PhD, Address: Department of Information Physiology, National Institute for Physiological Sciences, Okazaki, Japan., E-mail: furue@ 123456nips.ac.jp
                Article
                bcn-8-37
                10.15412/J.BCN.03080105
                5396171
                28446948
                979b84c7-b093-427e-9e80-f443ff376d4e
                Copyright© 2017 Iranian Neuroscience Society

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 17 June 2016
                : 03 November 2016
                : 29 November 2016
                Categories
                Research Papers

                formalin test,hairy skin,glabrous skin,tonic pain,nociception

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