Peripheral antihyperalgesic and analgesic actions of ketamine and amitriptyline in a model of mild thermal injury in the rat.
In this study, we examined antihyperalgesic and analgesic actions after local peripheral administration of ketamine and amitriptyline in a rat model of mild thermal injury. Exposure of the hindpaw to 52 degrees C for 45 s under anesthesia produced a subsequent thermal hyperalgesia lasting at least 2 h. The local peripheral administration of ketamine (100-1000 nmol) 15 min before the thermal injury produced an antihyperalgesic effect when injected into the ipsilateral paw, whereas amitriptyline produced both antihyperalgesic (300 nmol) and analgesic (1000 nmol) effects. Administered after the thermal injury, ketamine had no effect, whereas amitriptyline retained its analgesic but not its antihyperalgesic effect. Amitriptyline (300 and 1000 nmol) produced an analgesic action when administered into the normal nonsensitized hindpaw. Both drugs increase paw volume, particularly at larger doses; biogenic amines are not involved in the action of amitriptyline, as was shown previously for ketamine. These results indicate that (a) ketamine produces antihyperalgesia, but not analgesia, when administered locally with a mild thermal injury model; (b) amitriptyline produces both antihyperalgesia and analgesia when administered locally; and (c) the increase in paw volume produced by these drugs occurs by different mechanisms.


CONCLUSIONS
This study examines the pain-relieving properties of the local peripheral administration of ketamine and amitriptyline, two drugs in current clinical use, in a thermal injury model of hyperalgesia and demonstrates both antihyperalgesic and analgesic properties. These observations provide support for their potential use as local (e.g., topical) analgesics.
Oatway
Mark
M
Department of Pharmacology, Dalhousie University, Halifax, Nova Scotia, Canada.
Reid
Allison
A
Sawynok
Jana
J
D000287:Administration, Topical; D000639:Amitriptyline / Q000627:therapeutic use*; D000778:Anesthetics, Dissociative / Q000627:therapeutic use*; D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000627:therapeutic use*; D002056:Burns / Q000150:complications*; D004305:Dose-Response Relationship, Drug; D004487:Edema / Q000473:pathology; D005528:Foot; D006930:Hyperalgesia / Q000188:drug therapy* / Q000209:etiology*; D007267:Injections; D007649:Ketamine / Q000627:therapeutic use*; D008297:Male; D017288:Pain Threshold / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley
D000778:Anesthetics, Dissociative; D000929:Antidepressive Agents, Tricyclic; D000639:Amitriptyline; D007649:Ketamine