Delta-opioid receptors are critical for tricyclic antidepressant treatment of neuropathic allodynia.
BACKGROUND
The therapeutic effect of antidepressant drugs against depression usually necessitates a chronic treatment. A large body of clinical evidence indicates that antidepressant drugs can also be highly effective against chronic neuropathic pain. However, the mechanism by which these drugs alleviate pain is still unclear.


METHODS
We used a murine model of neuropathic pain induced by sciatic nerve constriction to study the antiallodynic properties of a chronic treatment with the tricyclic antidepressants nortriptyline and amitriptyline. Using knockout and pharmacological approaches in mice, we determined the influence of delta-opioid receptors in the therapeutic action of chronic antidepressant treatment.


RESULTS
In our model, a chronic treatment by tricyclic antidepressant drugs totally suppresses the mechanical allodynia in neuropathic C57Bl/6J mice. This therapeutic effect can be acutely reversed by an injection of the delta-opioid receptor antagonist naltrindole. Moreover, the antiallodynic property of antidepressant treatment is absent in mice deficient for the delta-opioid receptor gene.


CONCLUSIONS
The antiallodynic effect of chronic antidepressant treatment is mediated by a recruitment of the endogenous opioid system acting through delta-opioid receptors.
Benbouzid
Malika
M
Institut des Neurosciences Cellulaires et Intégratives, Centre National de Recherche Scientifique/Université Louis Pasteur, Strasbourg, France.
Gavériaux-Ruff
Claire
C
Yalcin
Ipek
I
Waltisperger
Elisabeth
E
Tessier
Luc-Henri
LH
Muller
André
A
Kieffer
Brigitte L
BL
Freund-Mercier
Marie José
MJ
Barrot
Michel
M
D000639:Amitriptyline / Q000494:pharmacology*; D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009437:Neuralgia / Q000188:drug therapy*; D009661:Nortriptyline / Q000494:pharmacology*; D017465:Receptors, Opioid, delta / Q000187:drug effects* / Q000235:genetics*; D012585:Sciatica / Q000188:drug therapy
D000929:Antidepressive Agents, Tricyclic; D017465:Receptors, Opioid, delta; D000639:Amitriptyline; D009661:Nortriptyline