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      Epinephrine, phenylephrine, and methoxamine induce infiltrative anesthesia via α1-adrenoceptors in rats

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          To assess whether epinephrine, phenylephrine, and methoxamine act via certain subtypes of adrenoceptors to exert their local anesthetic activity.


          We investigated cutaneous anesthesia from adrenoceptor agonists and/or antagonists in conscious, unanesthetized Sprague-Dawley male rats (weight 200−250 g). Cutaneous anesthesia was evidenced by a block of the cutaneous trunci muscle reflex, which is characterized by reflex movement of the skin over the back produced by twitches of lateral thoracispinal muscles in response to local dorsal cutaneous noxious pinprick.


          Local infiltration of epinephrine, L-phenylephrine, or methoxamine alone induces cutaneous anesthesia in rats in a dose-dependent way. Epinephrine is found to be 19 and 29 times more potent than those of methoxamine and L-phenylephrine, respectively. The cutaneous anesthesia induced by epinephrine, phenylephrine, or methoxamine can be significantly reduced by α 1-adrenoceptor antagonists ( eg, prazosin), α1, α2-adrenoceptor antagonist, α 1A-adrenoceptor antagonist ( eg, 5-methylurapdil), α 1B-adrenoceptor antagonist (eg, chloroethylclonidine), or α 1D-adrenoceptor antagonist ( eg, BMY7873).


          Our results indicate that epinephrine, phenylephrine and methoxamine all act mainly via mixed subtypes of α 1-adrenoceptors to induce cutaneous anesthesia in the rat.

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          Most cited references 33

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          Dexmedetomidine enhances the local anesthetic action of lidocaine via an alpha-2A adrenoceptor.

          Clonidine, an alpha-2 adrenoceptor agonist, is a common adjunct in both central and peripheral blocks. Dexmedetomidine, a more selective alpha-2 adrenoceptor agonist, is also known to enhance central neural blockades. Its peripheral effect, however, has not been fully elucidated. Thus, we evaluated the effect of dexmedetomidine and other alpha-2 adrenoceptor agonists on the local anesthetic action of lidocaine at the periphery and explored the mechanism involved. alpha-2 Adrenoceptor agonists, including dexmedetomidine, clonidine, and oxymetazoline, combined with lidocaine were intracutaneously injected into the back of male guinea pigs. The test of six pinpricks was applied every 5 min until 60 min after the injection. The number of times which the prick failed to elicit a response during the 60-min period was added and the sum served as an anesthetic score indicating the degree of local anesthesia. Differences from the control value within the group were analyzed using an analysis of variance followed by a post hoc Dunnett's test. Furthermore, we evaluated the antagonism of the effect of dexmedetomidine by yohimbine, an alpha-2A, 2B, and 2C adrenoceptor antagonist, or prazosin, an alpha-1, alpha-2B, and 2C adrenoceptor antagonist, analyzed using a two-way analysis of variance. All alpha-2 adrenoceptor agonists enhanced the degree of local anesthesia of lidocaine in a dose-dependent manner. Furthermore, yohimbine inhibited the effect of dexmedetomidine, whereas prazosin did not. We demonstrated that alpha-2 adrenoceptor agonists enhanced the local anesthetic action of lidocaine, and suggest that dexmedetomidine acts via alpha-2A adrenoceptors.
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            Comparison of three rodent neuropathic pain models

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              Topical application of clonidine relieves hyperalgesia in patients with sympathetically maintained pain.

              Patients with reflex sympathetic dystrophy or causalgia characteristically have ongoing pain and pain to light touch (hyperalgesia). Some of these patients obtain relief of their pain following interruption of sympathetic function to the affected area and, therefore, have sympathetically maintained pain (SMP). Evidence suggests that the pain and hyperalgesia in SMP are related to activation of peripheral adrenergic receptors. We wished to determine the contribution of alpha 1- and alpha 2-adrenergic receptors in SMP and thus examined the effects of local application of adrenergic agents in patients with SMP. The alpha 2-adrenergic agonist clonidine, available as a transdermal patch, was delivered topically to the patients' hyperalgesic skin. In four patients with SMP, clonidine eliminated or substantially reduced hyperalgesia to mechanical and cold stimuli. In three of these patients the effects were confined to the skin region beneath the patch, suggesting a peripheral and not central effect. The relief of hyperalgesia was not due to a local anesthetic effect since touch thresholds were unaffected. Topical clonidine did not relieve hyperalgesia of similar severity for two other patients whose hyperalgesia and pain were unaffected by sympathetic ganglion blocks (i.e., diagnosed as having sympathetically independent pain). In two SMP patients, intradermal injection of norepinephrine or phenylephrine (a specific alpha 1-adrenergic agonist) at a site treated with clonidine evoked intense pain and rekindled the pre-clonidine hyperalgesia at that site. It is likely that clonidine locally blocks the release of norepinephrine via activation of alpha 2 receptors on the sympathetic terminals. This study suggests, therefore, that SMP is mediated via alpha 1-adrenergic receptors located in the affected tissue.

                Author and article information

                Acta Pharmacol Sin
                Acta Pharmacol. Sin
                Acta Pharmacologica Sinica
                Nature Publishing Group
                September 2009
                04 September 2009
                : 30
                : 9
                : 1227-1236
                [1 ]Department of Anesthesiology, Chi Mei Medical Center , Tainan, Taiwan, China
                [2 ]Department of Medical Research, Chi Mei Medical Center , Tainan, Taiwan, China
                Author notes
                Copyright © 2009 CPS and SIMM
                Original Article


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