Assessing carrageenan-induced locomotor activity impairment in rats: comparison with evoked endpoint of acute inflammatory pain.

Abstract

BACKGROUND:

Most animal models currently used to evaluate antinociceptive efficacy of analgesics rely on the assessment of evoked pain behaviours as primary endpoints.

METHODS:

Here, we have developed and characterized the carrageenan-induced locomotor activity impairment (CLAIM) model to objectively assess non-evoked inflammatory pain behaviour in rats. In this model, 100 µL of 1% carrageenan was subcutaneously injected into the plantar aspect of the right hind paw and exploratory behaviour in the novel testing chamber was recorded using an automated locomotor activity system.

RESULTS:

Carrageenan-injected animals exhibited an exploratory behavioural deficit 2-7 h following injection compared to saline-injected animals. The severity of impairment was carrageenan dose related, and sensitive to the light intensity in the testing room. The effects of standard analgesics on CLAIM were examined 2 or 3 h following carrageenan injection. Diclofenac and ibuprofen, in a dose range exerting no effect on locomotor activity in naïve rats, exhibited dose-related reversal of CLAIM (ED(50) = 1.5 and 5.0 mg/kg, respectively), with comparable efficacy on carrageenan-induced thermal hyperalgesia (ED(50) = 2.0 and 6.0 mg/kg, respectively). Gabapentin and duloxetine produced no reversal of CLAIM, or attenuation of thermal hyperalgesia. Efficacy discrepancy was noted for morphine on thermal hyperalgesia and CLAIM. Additionally, amphetamine dose dependently reversed CLAIM, and similarly increased locomotor activity in normal animals.

DISCUSSION AND CONCLUSION:

The results presented here demonstrate that CLAIM provides an objective assessment of non-evoked pain behaviours for acute inflammatory pain. The pharmacological profile of standard analgesics supports that CLAIM model can be used to identify agents to treat acute inflammatory pain in the clinic.

• Authors: C Z Zhu, C D Mills, G C Hsieh, C Zhong, J Mikusa, L G Lewis, D Gauvin, C-H Lee, M W Decker, A W Bannon, L E Rueter, S K Joshi
• Journal: European journal of pain (London, England) (Eur J Pain) Vol. 16 Issue 6 Pg. 816-26 (Jul 2012) ISSN: 1532-2149 [Electronic] England
• PMID: 22337256 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2012 European Federation of International Association for the Study of Pain Chapters.

Chemical References

• Adrenergic Uptake Inhibitors
• Amines
• Analgesics
• Analgesics, Opioid
• Anti-Inflammatory Agents, Non-Steroidal
• Central Nervous System Stimulants
• Cyclohexanecarboxylic Acids
• Thiophenes
• Diclofenac
• gamma-Aminobutyric Acid
• Gabapentin
• Morphine
• Carrageenan
• Duloxetine Hydrochloride
• Amphetamine
• Ibuprofen

Topics

• Acute Pain (chemically induced, drug therapy, physiopathology)
• Adrenergic Uptake Inhibitors (pharmacology)
• Amines (pharmacology)
• Amphetamine (pharmacology)
• Analgesics (pharmacology)
• Analgesics, Opioid (pharmacology)
• Animals
• Anti-Inflammatory Agents, Non-Steroidal (pharmacology)
• Behavior, Animal (drug effects, physiology)
• Carrageenan (pharmacology)
• Central Nervous System Stimulants (pharmacology)
• Cyclohexanecarboxylic Acids (pharmacology)
• Diclofenac (pharmacology)
• Disease Models, Animal
• Duloxetine Hydrochloride
• Gabapentin
• Hyperalgesia (chemically induced, drug therapy, physiopathology)
• Ibuprofen (pharmacology)
• Lameness, Animal (chemically induced, drug therapy, physiopathology)
• Male
• Morphine (pharmacology)
• Motor Activity (drug effects, physiology)
• Neuritis (chemically induced, drug therapy, physiopathology)
• Rats
• Rats, Sprague-Dawley
• Thiophenes (pharmacology)
• gamma-Aminobutyric Acid (pharmacology)