Unilateral intramuscular injections of acidic saline produce a bilateral, long-lasting hyperalgesia

Muscle Nerve. 2001 Jan;24(1):37-46. doi: 10.1002/1097-4598(200101)24:1<37::aid-mus4>3.0.co;2-8.


This study characterizes an animal model of persistent mechanical hyperalgesia induced by repeated intramuscular injections of low pH saline. Saline at pH 4, 5, 6, or 7.2 was injected twice, 2 to 10 days apart, into the gastrocnemius muscle of rats. To quantify hyperalgesia, paw withdrawal latency to radiant heat (heat hyperalgesia) and withdrawal threshold to mechanical stimuli (mechanical hyperalgesia) were measured. Two unilateral injections of low pH saline, 5 days apart, caused a pH-dependent bilateral mechanical, but not heat, hyperalgesia that lasted 30 days. Injections given 2 and 5 days apart produced a significantly greater mechanical hyperalgesia than injections given 10 days apart. Lidocaine injection into the gastrocnemius muscle or unilateral dorsal rhizotomy, 24 h after the second injection (pH 4), had no effect on the contralateral mechanical hyperalgesia. Minimal histopathology was observed in the injected muscle, and changes were similar between groups injected with pH 4 and pH 7.2. Thus, this new model of widespread, chronic muscle-induced pain is unrelated to tissue damage and is not maintained by continued primary afferent input from the site of injury.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Behavior, Animal / drug effects
  • Behavior, Animal / physiology
  • Body Weight / drug effects
  • Coloring Agents
  • Disease Models, Animal
  • Drug Combinations
  • Evans Blue
  • Functional Laterality / drug effects*
  • Hot Temperature
  • Hydrochloric Acid / administration & dosage*
  • Hydrogen-Ion Concentration / drug effects
  • Hyperalgesia / chemically induced*
  • Hyperalgesia / physiopathology*
  • Injections, Intramuscular
  • Male
  • Motor Activity / drug effects
  • Motor Activity / physiology
  • Muscle, Skeletal / drug effects
  • Muscle, Skeletal / metabolism
  • Muscle, Skeletal / pathology
  • Muscle, Skeletal / physiopathology
  • Pain Measurement / drug effects
  • Physical Stimulation
  • Rats
  • Rats, Sprague-Dawley
  • Reaction Time / drug effects
  • Sodium Chloride / administration & dosage*


  • Coloring Agents
  • Drug Combinations
  • Sodium Chloride
  • Evans Blue
  • Hydrochloric Acid