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Intraarticular Mechanisms for Pain Control

Postoperative pain control after surgery of the joint can be obtained through the use of intraarticular injection of local anesthetics and opioids.
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The observation that patients who had arthroscopic knee surgery under local anesthesia seem to have less postoperative pain than patients with comparable procedures performed under general anesthesia lead to investigations to explain this phenomenon. A similar favorable effect was noted after general anesthesia if the intraarticular local anesthetic solution was injected as a part of the arthroscopic surgery. The idea that postoperative analgesia could be achieved by injection of local anesthetics and/or opiates into the joint prior to surgery was considered a possible explanation.

Clinical Studies of Intraarticular Analgesia

The first clinical study of intraarticular pain control was reported by Stein.1 There were 52 patients with morphine, saline and naloxone injected into the intraarticular space at the conclusion of surgery. The dose of morphine was very small (1mg) and provided complete pain relief for up to 18 hours after intraarticular arthroscopic surgery of the knee. This pain control was not achieved by intravenous morphine either in quality or duration and was eliminated when naloxone was injected into the intraarticular space. A dose of 0.5 mg of morphine was analgesic but not as effective as 1.0 mg. Khouri2 evaluated morphine, bupivacaine or a combination after surgical arthroscopy and found the combination to be superior to either element alone, when injected at the conclusion of surgery. Allen3 also looked at surgical arthroscopy, and found the combination of bupivacaine (0.125 percent), morphine and epinephrine to be the best choice, with nearly complete pain control for up to 24 hours. De Andres4 compared postoperative intraarticular bupivacaine or morphine with femoral nerve block and found the intraarticular injection to provide comparable analgesia to femoral nerve block. With non-arthroscopic ACL repair, intraarticular morphine was significantly better than saline administered at the conclusion of surgery, injected by needle away from the wound after the joint was sealed and the drain clamped.5-6

“Intraarticular local anesthetics alone have been shown to have an analgesic effect postoperatively.”

Intraarticular local anesthetics alone have been shown to have an analgesic effect postoperatively. Gyrn7 reported an improvement of pain control with increasing doses of bupivacaine and epinephrine given as the sole anesthetic for diagnostic arthroscopy. The favorable effect is not limited to bupivacaine, with prilocaine plus epinephrine being superior to saline for pain control administered into the intraarticular space at the conclusion of surgical arthroscopy.8 Badner injected 0.5 percent bupivacaine into the knee joint at the completion of total knee replacement and found analgesia, reduced opioid requirements and some improvement in early joint mobility.9 Badner also added epinephrine to intraarticular bupivacaine and demonstrated analgesia after total knee replacement, which did not improve with the addition of morphine.10 Although some pain relief could be demonstrated with intraarticular bupivacaine without epinephrine, intraarticular morphine was superior.11-12 For limited procedures, intraarticular lidocaine was equivalent to femoral nerve block.13

Intraarticular analgesia has also been demonstrated with other substances besides opioids and local anesthetics. Badner demonstrated an analgesic effect with epinephrine,10 which was also noted by Gatt.14 Other intraarticular analgesic effects have been demonstrated with NSAIDs,15-17 neostigmine18 and steroids.19

Raja,20 Bjornsson21 and Heard22 report inconclusive data although study design description does not allow evaluation of surgical technique variation that could explain the conflicting outcome. In particular, it is impossible to tell if the solutions were injected after the knee was watertight. Whitford demonstrated a beneficial effect of intraarticular injection during tourniquet inflation, which did not occur when the injection occurred immediately before tourn-iquet deflation.23 Reuben could not demonstrate an additional benefit after minor arthroscopic surgery from intraarticular morphine when it was added to intraarticular bupivacaine and systemic keterolac,24 possibly because bupivacaine combined with systemic keterolac was completely analgesic.

Cellular Mechanisms for Intraarticular Pain Control

Although it is widely accepted that opioids produce analgesia by activation of opioid receptors at the spinal and supraspinal levels, there is increasing speculation about activity of opioids at peripheral sites. Animal studies suggest the possibility of a direct effect in peripheral tissue. Joris25 reported a study involving rats and a standard inflammatory process. After injecting an irritating agent into both paws and allowing the correct interval for development of hyperalgesia, either fentanyl or another opioid agonist was injected into the inflamed site of one paw and saline into the other. Significantly less hyperalgesia evolved in the opioid injected paw. Ferreira26 found a similar effect, which was not reversible by naloxone after morphine. Calcium ion movement was shown to be related to the development of hyperalgesia and analgesia during the same experiments.27 Stein28 was able to demonstrate peripheral opioid receptors in rats with acute inflammation. These receptors were induced by inflammation, since they were not present in normal (non-inflamed) tissues.

Last updated on: December 27, 2012
First published on: September 1, 2000