Differential analgesic sensitivity of two distinct neuropathic pain models.
Progressive tactile hypersensitivity (PTH) manifesting after sciatic nerve crush and spared nerve injury (SNI) are two distinct rodent experimental models of neuropathic pain. PTH develops months after recovery from the nerve crush in response to repeated intermittent low-threshold mechanical stimulation of the reinnervated sciatic nerve skin territory and represents a model of stimulus-induced pain. SNI is characterized by an early and sustained increase in stimulus-evoked pain sensitivity in the intact skin territory of the spared sural nerve after sectioning of the two other terminal branches of the sciatic nerve. We examined the effects of morphine (0.5-10 mg/kg), gabapentin (30-200 mg/kg), MK801 (0.01-0.02 mg/kg), amitriptyline (10-25 mg/kg), and carbamazepine (5-7.5 mg/kg) in both models. Morphine, gabapentin, and carbamazepine both reversed and prevented stimulus-induced PTH, whereas MK801 and amitriptyline reduced but did not prevent stimulus-induced PTH. In contrast, the stimulus-evoked behavioral hypersensitivity in the SNI model was poorly modified by these drugs. Independent neuropathic pain models show differential sensitivity to analgesic drug treatment. We suggest that this is due to the different mechanisms responsible for the neuropathic pain-related behavior. Multiple models are required, therefore, to study the mechanisms that contribute to neuropathic pain and to predict analgesic efficacy for different components of the neuropathic pain syndrome.
Anesthesiology Pain Research Group, Department of Anesthesiology & DBCM, University of Lausanne, Bugnon 9, 1005 Lausanne, Switzerland. Isabelle.Decosterd@chuv.hospvd.ch
Isabelle
I
Decosterd
Andrew
A
Allchorne
Clifford J
CJ
Woolf
D000085:Acetates / Q000627:therapeutic use; D000588:Amines; D000700:Analgesics / Q000627:therapeutic use*; D000701:Analgesics, Opioid / Q000627:therapeutic use; D000818:Animals; D003080:Cold Temperature; D003509:Cyclohexanecarboxylic Acids; D004195:Disease Models, Animal; D016291:Dizocilpine Maleate / Q000627:therapeutic use; D000077206:Gabapentin; D006358:Hot Temperature; D006930:Hyperalgesia / Q000517:prevention & control; D008297:Male; D009020:Morphine / Q000627:therapeutic use; D009409:Nerve Crush; D018696:Neuroprotective Agents / Q000627:therapeutic use; D010146:Pain / Q000188:drug therapy* / Q000209:etiology*; D010147:Pain Measurement / Q000187:drug effects; D010523:Peripheral Nervous System Diseases / Q000150:complications*; D010812:Physical Stimulation; D051381:Rats; D017207:Rats, Sprague-Dawley; D020426:Sciatic Neuropathy / Q000150:complications; D005680:gamma-Aminobutyric Acid
D000085:Acetates; D000588:Amines; D000700:Analgesics; D000701:Analgesics, Opioid; D003509:Cyclohexanecarboxylic Acids; D018696:Neuroprotective Agents; D005680:gamma-Aminobutyric Acid; D000077206:Gabapentin; D016291:Dizocilpine Maleate; D009020:Morphine