Ankle joint mobilization decreases hypersensitivity by activation of peripheral opioid receptors in a mouse model of postoperative pain

Pain Med. 2012 Aug;13(8):1049-58. doi: 10.1111/j.1526-4637.2012.01438.x. Epub 2012 Jul 9.


Objective: Investigate whether ankle joint mobilization (AJM) decreases hypersensitivity in the mouse plantar incision (PI) model of postoperative pain as well as to analyze the possible mechanisms involved in this effect.

Design: Experiment 1: PI male Swiss mice (25-35 g, N = eight animals per group) were subjected to five sessions of AJM, each lasting either 9 or 3 minutes. AJM movement was applied at a grade III as defined by Maitland. Paw withdrawal frequency to mechanical stimuli was assessed before realization of PI and before and after daily AJM sessions. Mechanical hypersensitivity was also assessed following systemic (intraperitoneal [i.p.]) and local (intraplantar) injection of naloxone (a nonselective opioid receptor antagonist; 1 mg/kg, i.p.; 5 µg/paw, respectively, experiment 2); and systemic injection of fucoidin (100 µg/mouse, i.p., an inhibitor of leukocyte rolling, experiment 3) in different groups of mice.

Results: Nine but not 3 minutes of AJM reduced mechanical hypersensitivity caused by PI, an effect that was prevented by systemic and local administrations of naloxone but not by fucoidin.

Conclusions: Our results indicate that joint mobilization reduces postoperative pain by activation of the peripheral opioid pathway. However, antihypersensitivity induced by AJM is apparently not limited by the number of opioid-containing leukocytes but by opioid receptors availability in sensory neurons. A better understanding of the peripheral mechanisms of AJM could stimulate therapists to integrate joint mobilization with strategies also known to influence endogenous pain control, such as exercise, acupuncture, and transcutaneous electrical nerve stimulation to potentiate endogenous analgesia.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Ankle Joint / innervation*
  • Ankle Joint / physiology
  • Disease Models, Animal
  • Hyperalgesia / drug therapy
  • Hyperalgesia / rehabilitation
  • Hyperalgesia / therapy*
  • Male
  • Mice
  • Musculoskeletal Manipulations / methods*
  • Pain, Postoperative / drug therapy
  • Pain, Postoperative / rehabilitation
  • Pain, Postoperative / therapy*
  • Receptors, Opioid / physiology*


  • Receptors, Opioid