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Considering the Long-Term Effects of Pain on Patient Outcomes During the Postoperative Recovery Period

Commentary on an article by Brian J. Loyd, PT, PhD, et al.: “Peripheral Nociception Is Associated with Voluntary Activation Deficits and Quadriceps Weakness Following Total Knee Arthroplasty”

Osman, Brian M. MD

doi: 10.2106/JBJS.19.00684
Commentary and Perspective
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Department of Anesthesiology, Perioperative Medicine and Pain Management, University of Miami Miller School of Medicine, Miami, Florida

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Disclosure: The author indicated that no external funding was received for any aspect of this work. The Disclosure of Potential Conflicts of Interest form is provided with the online version of the article (

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In this Level-IV study, Loyd et al. assert that peripheral nociception is associated with voluntary quadriceps weakness following total knee arthroplasty. This builds on prior evidence and opens up an excellent discussion on the role of central nociception compared with peripheral nociception and their effects on long-term patient outcomes. The idea encourages an important collaboration between orthopaedic surgeons and anesthesiologists for targeting the best pain therapies following total knee arthroplasty. Are systemic, centrally acting techniques better? Or are local or peripheral techniques better? How about both? Consider the side effects. The authors recognize the role of nociception in long-term patient outcomes and emphasize the importance of tailoring multimodal pain management during the recovery phase after total knee arthroplasty.

Loyd et al. mention that profound postoperative quadriceps weakness and atrophy are a major concern that limits recovery, diminishes function, and increases the risk of injury to the patient because of instability and falls. The etiology of this prolonged postoperative weakness is elusive, but appropriate mention is given to other investigations that have suggested that the etiology for muscle weakness after total knee arthroplasty is related to nociception and pain and reduced voluntary muscle activation. The idea is that deliberate and reduced use of this large muscle group to avoid pain will eventually result in the atrophy and weakness described by both the literature and the authors. That is to say, if you don’t use it, you lose it. Although nociception is a likely known culprit for causing postoperative quadriceps weakness, quantifying it and questioning central nociceptor activation compared with peripheral nociceptor activation is an interesting and novel concept.

The authors of this study suggest that measuring muscle activation using the maximum voluntary isometric contraction has proven to be quite reliable in patients following total knee arthroplasty, but attempting to quantify pain can be more problematic. The experience is very personal, involves complicated pathways, and can be very subjective. Additionally, nociception, or the process by which tissue damage is relayed to the brain, can be entirely independent of pain perception. The current study uses an interesting method to quantify nociceptor sensitization by measuring the pressure-pain thresholds in their subjects. However, it appears that all of the study participants received treatments that would affect both the peripheral and central pain pathways (i.e., centrally acting pain medications such as acetaminophen, pregabalin, and meloxicam compared with peripherally acting techniques such as peripheral nerve blocks and periarticular injections), rendering differentiation of the pathways impossible. Using the pressure-pain thresholds would be a good way to assess an individual patient’s baseline for pain perception and tolerance but would not speak to central mechanisms compared with peripheral mechanisms for nociception.

The major conclusion of this study, adding to prior investigations, is that nociception and the mediation effect of reduced voluntary activation both can contribute to quadriceps weakness following total knee arthroplasty. The study also mentions that the data examine local or systemic nociception in relation to strength or activation, specifically stating that there was no significant relationship between the change in forearm pressure-pain thresholds and change in quadriceps strength and activation. Although bringing up the obvious limitations of this observational study, the authors mention that these data could be interpreted to mean that central nociceptive mechanisms are not implicated in strength recovery after a surgical procedure. This is an oversimplification of the pain pathways. Eliciting pain from another peripheral site (i.e., the forearm) does not qualify solely as a central nociceptor mechanism. The forearm may not be the site of the surgical procedure, but the pressure-pain threshold still provides stimulation of peripheral nociceptors that are attached to thin myelinated Aδ and unmyelinated C fibers, terminating in the dorsal horn of the spine. If the pressure-pain threshold test pushes hard enough, then the peripheral inflammatory and biomolecular influences come into play. The next logical step in comparing central pain sensitization with peripheral pain sensitization would be to isolate the subjects into 2 different arms of the study, with 1 group receiving only peripheral treatments (i.e., cryotherapy and peripheral nerve blocks) and the other group receiving central treatments (neuraxial anesthesia, ketamine, centrally acting pain medications), and to compare the muscle activation by the maximum voluntary isometric contraction in those groups.

Overall, the study is interesting, and although enlarging the body of evidence that supports peripheral sensitization as a mechanism of postoperative quadriceps strength loss, the authors are attempting to focus the magnifying glass on which component of the pain process (peripheral compared with central) is contributing most to this problem. The authors are onto something here. It is a crucial topic for guiding current multimodal analgesia regimens as well as the protocols related to enhanced recovery after surgery.

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