Translation of the rat thoracic contusion model; part 1-supraspinally versus spinally mediated pain-like responses and spasticity

Spinal Cord. 2014 Jul;52(7):524-8. doi: 10.1038/sc.2014.72. Epub 2014 May 13.

Abstract

Study design: Experimental animal study.

Objectives: Stimulus-evoked below-level paw withdrawals in animal models of spinal cord injury (SCI) can be mediated solely by below-level spinal cord reflexes. Interpreting lowered thresholds for such responses as a model for chronic below-level pain after (thoracic contusion) SCI appears not appropriate, which requires reinterpretation of many prior results. However, how to reinterpret the changes in withdrawal thresholds and what can be a better alternative for pain/sensory assessments remains unclear.

Setting: University of California, San Diego.

Methods: We introduce a method using supraspinally mediated escape responses to assess pain-like sensitivity thresholds on a continuous/linear scale. To further understand the decrease in hindpaw withdrawal thresholds, we investigated whether they may be interpreted as spasticity.

Results: The escape response test can be used to assess SCI-induced changes in below-level sensory thresholds. These thresholds were found to increase soon after moderate or severe SCI, while, in parallel, hindpaw withdrawal thresholds decreased. However, the latter did not co-occur with spasticity, suggesting that SCI-induced increased withdrawal responses are probably best interpreted as a form of hyperreflexia with pathophysiological analogies of spasms and/or clonus, or a species-specific phenomenon.

Conclusion: Decreased below-level withdrawal thresholds do not reflect pain-like hypersensitivity in rodent models of (thoracic contusion) SCI. A large body of previous preclinical SCI pain research needs reinterpretation. We actually found below-level thermal and mechanical hypoesthesia and we also excluded a relation between withdrawal hyperreflexia and spasticity. Withdrawal hyperreflexia might still prove useful to model spasms or clonus, which are, like hypoesthesia, also significant clinical problems after SCI.

MeSH terms

  • Animals
  • Brain / physiopathology*
  • Disease Models, Animal
  • Escape Reaction / physiology
  • Female
  • Hindlimb / physiopathology
  • Muscle Spasticity / physiopathology*
  • Pain / physiopathology*
  • Pain Measurement
  • Pain Threshold
  • Rats, Sprague-Dawley
  • Reflex, Stretch / physiology
  • Severity of Illness Index
  • Spinal Cord / physiopathology*
  • Spinal Cord Injuries / physiopathology*