Dataset Information

Beta2-adrenoceptor agonists alleviate neuropathic allodynia in mice after chronic treatment.

ABSTRACT:

Background and purpose

Antidepressants are a first-line treatment against neuropathic pain. We previously demonstrated that beta(2)-adrenoceptors are necessary for antidepressants to exert their anti-allodynic action. The aim of the present study was to assess whether beta(2)-adrenoceptor agonists could be sufficient to alleviate neuropathic allodynia.

Experimental approach

We used a murine model of neuropathy induced by unilateral sciatic nerve cuffing in C57BL/6J mice. We previously demonstrated that this animal model is sensitive to chronic, but not to acute, treatment with antidepressant drugs, which is clinically relevant. The mechanical allodynia was evaluated using the von Frey filaments.

Key results

We showed that chronic but not acute treatment with the beta-adrenoceptor agonists, bambuterol, isoprenaline, fenoterol, salbutamol, salmeterol, terbutaline or ritodrine suppressed mechanical allodynia. We confirmed that the action of these beta-adrenoceptor agonists was mediated through beta(2)-adrenoceptors by blocking it with intraperitoneal or intrathecal, but not intracerebroventricular or intraplantar, injections of the antagonist ICI118551. We also showed that chronic treatments with the beta-adrenoceptor antagonists, propranolol or ICI118551 did not suppress the allodynia.

Conclusions and implications

Our data show that chronic treatment with beta-adrenoceptor agonists has the same antiallodynic properties as treatments with antidepressant drugs. This study was, however, conducted in an animal model, and a clinical validation will be required to confirm the value of the present findings in patients.

SUBMITTER: Choucair-Jaafar N

PROVIDER: S-EPMC2801209 | biostudies-literature | 2009 Dec

REPOSITORIES: biostudies-literature

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Publications

Beta2-adrenoceptor agonists alleviate neuropathic allodynia in mice after chronic treatment.

Choucair-Jaafar Nada N Yalcin Ipek I Rodeau Jean-Luc JL Waltisperger Elisabeth E Freund-Mercier Marie-José MJ Barrot Michel M

British journal of pharmacology 20091201 7

<h4>Background and purpose</h4>Antidepressants are a first-line treatment against neuropathic pain. We previously demonstrated that beta(2)-adrenoceptors are necessary for antidepressants to exert their anti-allodynic action. The aim of the present study was to assess whether beta(2)-adrenoceptor agonists could be sufficient to alleviate neuropathic allodynia.<h4>Experimental approach</h4>We used a murine model of neuropathy induced by unilateral sciatic nerve cuffing in C57BL/6J mice. We previo ...[more]

PMID: 19912227

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Project description:1 The principal aim of the present study was to determine whether long-term treatment of human lung mast cells (HLMC) with the clinically-relevant beta(2)-adrenoceptor agonists, salbutamol and terbutaline, leads to desensitization of beta(2)-adrenoceptor-mediated responses in these cells. 2 The non-selective beta-adrenoceptor agonist, isoprenaline, and the selective beta(2)-adrenoceptor agonists, salbutamol and terbutaline, inhibited the IgE-mediated release of histamine from HLMC. Salbutamol (pD(2); 7.7+/-0.3) and terbutaline (pD(2); 7.3+/-0.2) were roughly equipotent as inhibitors of histamine release although both agonists were less potent than isoprenaline (pD(2); 8.6+/-0.2). 3 Isoprenaline (10(-5) M), salbutamol (10(-5) M) and terbutaline (10(-5) M) enhanced total cell cAMP levels in HLMC over basal by 361+/-90, 150+/-38 and 165+/-35%, respectively. 4 Long-term exposure (24 h) of HLMC to either salbutamol (10(-7) M) or terbutaline (10(-7) M) led to a subsequent reduction in the effectiveness of salbutamol and terbutaline (both 10(-9)-10(-4) M) to inhibit histamine release. However, salbutamol was significantly (P<0.05) more effective than terbutaline at promoting the functional desensitization. 5 Radioligand binding studies, using iodinated cyanopindolol, were performed to determine beta(2)-adrenoceptor density in cell membranes after pretreatment (24 h) of cells with either salbutamol (10(-6) M) or terbutaline (10(-6) M). Both agonists reduced beta(2)-adrenoceptor density in membranes to about the same extent (approximately 25% reduction) but these changes in receptor density were not statistically significant (P>0.05). 6 These data indicate that long-term exposure of mast cells to salbutamol causes greater levels of desensitization to beta(2)-adrenoceptor-mediated responses in HLMC than terbutaline. These findings may have wider clinical significance in the context of asthma treatment as compromised mast cell inhibition could result following long-term exposure of mast cells to short-acting bronchodilators.

Dataset Information

Beta2-adrenoceptor agonists alleviate neuropathic allodynia in mice after chronic treatment.

Background and purpose

Experimental approach

Key results

Conclusions and implications

Publications

Beta2-adrenoceptor agonists alleviate neuropathic allodynia in mice after chronic treatment.

Similar Datasets

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