JACOB BEIRIGER, BS
ASIF ILYAS, MD, MBA, FACS
Early treatment with NSAIDs or steroids leads to prolonged pain following spine surgery.
Upregulation of a transient neutrophil inflammatory response is protective against progression to chronic pain.
The management of acute inflammation in the short term may lead to an increased risk of chronic pain.
Due to a massive 54% increase in lumbar spine surgery from 1999 to 2013, there has been an ever-growing need for physicians to manage both acute and chronic pain in a safe and effective way (1). Unfortunately, rates of complications also increased during this time from 0.7% to 2.4% (1). Because patients often experience severe pain for a minimum of three days following spinal surgery, sufficient postoperative pain management requires an informed and patient-centered approach (2). Adequate pain relief must also maximize the patient quality of life in both the short and long term. Pain management after spinal procedures has gained interest following a recent review of 179 surgeries where spinal procedures were among the top six with the highest degree of pain (3).
There has been an abundance of pain management strategies used in clinical practice following spinal surgery including parenteral approaches such as opioid analgesics, NSAIDs, ketamine, corticosteroids, intrathecal drug administration, epidural drug administration, alpha 2 adrenoreceptor antagonists, and transcutaneous electrical nerve stimulation (4). Additionally, hospital discharge rates associated with spinal fusion surgeries have increased by 137% in the last decade. Most of these are cervical and lumbar fusion. The purpose of this analysis is to present, discuss, and interpret clinical data concerning postoperative pain management strategies following spinal fusion, and highlight the short and long-term effects of pain management with NSAIDs.
Non-steroidal anti-inflammatory drugs (NSAIDs) have historically been useful in managing pain and incorporated into almost every regimen pertaining to postoperative management for spine surgery patients. Acetaminophen and paracetamol have been shown to decrease postoperative pain as well as opioid requirements compared to regimens with opioids alone for perioperative analgesia (5). However, there is concerns as to the possible impact NSAIDs have on osteogenesis and their risk of nonunion. One study found that ketorolac was avoided in postoperative pain management for fear of nonunion (Table 1) (6). This suggests that NSAIDs' anti-inflammatory profile may not be as beneficial to pain management as previously thought.
Table 1. Analysis of NSAIDs on Spinal Fusion. Reprinted from Li Q, Zhang Z, Cai Z. High-dose ketorolac affects adult spinal fusion: a meta-analysis of the effect of perioperative nonsteroidal anti-inflammatory drugs on spinal fusion. Spine. 2011;36(7):E461-8. doi:10.1097/BRS.0b013e3181dfd163
One study found reduced pain scores and decreased analgesic consumption with NSAID use, but did not evaluate the effect on bleeding risk, long-term spinal fusion, or bone healing for NSAIDs (7). This lack of detailed investigation on long-term NSAID effects illustrates a need for a review of pain regimens both in the short and long term.
Consideration of the side effect profile of NSAIDs on outcomes following spinal surgery is necessary. One meta-analysis utilized 17 studies to compare outcomes among patients treated with either NSAIDs alone or NSAIDs plus opioids following lumbar discectomy or laminectomy and spinal fusion (5). It found that the conjunctive therapy group reported lower visual analog scale (VAS) pain scores and consumed fewer opioids at two, six, 24, and 48 hours postoperatively. However, the statistically significant drop in the consumption of opioids did not yield a decrease in adverse effects (5). This begs the question of whether NSAIDs are the culprit for various adverse effects chronically seen.
One animal study looked at investigated the pathogenesis of chronic pain and the effects of anti-inflammatory medications on mice (Figure 1) (8). Evidence of interplay between the nervous and immune systems was seen, which led to the conclusion that chronic pain is a neuroinflammatory disorder mediated by neuronal and non-neuronal cells alike (9). Neutrophils, monocytes, and T cells are recruited to damaged tissue and inflammatory sites, and must subsequently infiltrate both the central and peripheral nervous systems to provide activation of responding cells. Activation then induces the expression of inflammatory mediators that contribute to pain sensation (10). Activation of immune cells and glia of the central and peripheral nervous systems is thought to be the mechanism behind the transition from acute to chronic pain (11).
Figure 1. Functional differences between the resolved and persistent pain groups. Reprinted from: Parisien M, Lima LV, Dagostino C, et al. Acute inflammatory response via neutrophil activation protects against the development of chronic pain. Science Translational Medicine. 2022;14(644). doi:10.1126/scitranslmed.abj9954
Research suggests that drugs interfering with inflammation may stunt the organic recovery process and increase the odds of developing chronic pain (8). One study compared the use of different analgesics including NSAIDs, acetaminophen, and antidepressants in acute low back pain. It determined that individuals with acute back pain had almost double the risk of developing chronic pain with reported NSAID use compared to those not taking NSAIDs (Figure 2) (8).
Figure 2. Impact of drug class on the development of chronic pain in humans. Reprinted from: Parisien M, Lima LV, Dagostino C, et al. Acute inflammatory response via neutrophil activation protects against the development of chronic pain. Science Translational Medicine. 2022;14(644). doi:10.1126/scitranslmed.abj9954
Postsurgical pain following spinal surgery is an extremely relevant issue in healthcare. Effective and adequate pain management is required to improve the functional outcomes of patients after surgery and facilitate discharge. Poorly managed postoperative pain contributes to longer hospital stays, slower progress in ambulation, respiratory complications, venous thrombosis, functional deficits, and increased cost of care (4).
While a multimodal analgesic strategy does appear to be the ideal strategy in practiced medicine today, there is an overarching lack of consensus and supporting data on the appropriate analgesic protocol or algorithm to maximize patient comfort, healing, and overall quality of life. More specifically, there exists a lack of investigation into chronic pain associated with NSAID usage in the face of present-day findings. Evidence-based evaluation of clinical data concerning NSAID prescription in regard to chronic pain will benefit both physicians and future research.
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6. Li Q, Zhang Z, Cai Z. High-dose ketorolac affects adult spinal fusion: a meta-analysis of the effect of perioperative nonsteroidal anti-inflammatory drugs on spinal fusion. Spine. 2011;36(7):E461-8. doi:10.1097/BRS.0b013e3181dfd163
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8. Parisien M, Lima LV, Dagostino C, et al. Acute inflammatory response via neutrophil activation protects against the development of chronic pain. Science Translational Medicine. 2022;14(644). doi:10.1126/scitranslmed.abj9954
9. Ji R-R, Chamessian A, Zhang Y-Q. Pain regulation by non-neuronal cells and inflammation. Science. 2016;354(6312):572-577. doi:10.1126/science.aaf8924
10. Kavelaars A, Heijnen CJ. Immune regulation of pain: Friend and foe. Sci Transl Med. 2021;13(619):eabj7152. doi:10.1126/scitranslmed.abj7152
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