Neurogenic and inflammatory signaling are the transmission pathways of surgical pain. Implementing multimodal pain management techniques to target both pathways is one of the biggest advances in arthroplasty surgery over the past decade.
There are significant side effects associated with over-reliance on narcotics for pain control including ileus, nausea, confusion, and lethargy, which can all contribute to a prolonged hospitalization and increase hospital re-admission, discharge to nursing facilities, and decrease patient satisfaction.
Pain management protocols are implemented the morning of surgery, during the surgery itself, and after surgery. They have been shown to shorten hospital stay, improve pain control and decrease opioid use while allowing successful recovery.
Peripheral signaling pathways (neurogenic and inflammatory) are triggered at the time of surgery and increase CNS sensitivity to pain stimuli. Preemptive analgesia can dampen the initial peripheral pain signal and prevent central hypersensitivity . Regional anesthesia (ie peripheral nerve blocks), local anesthesia (ie bupivicane infiltration around the surgical site), and systemic anesthesia (ie opioids) offer a robust approach to pain control in TJA. We will look at all of these pathways.
The multimodal regimen often begins in Preop Holding  where patients may receive a benzodiazepine, NSAID, and/or gabapentanoid. Patients are given regional anesthesia.
In THA either a spinal or epidural is utilized, while peripheral nerve blocks are reserved for TKA.
Regional Anesthesia. There is a trend to steer away from general anesthesia. Most arthroplasty procedures are performed with neuraxial (ie spinal and epidural) or regional (peripheral nerve blocks) anesthesia. The THA procedures benefit from spinal anesthesia or a lumbar epidural catheter in conjunction with propofol sedation. Avoiding general anesthesia has been shown to decrease post-op confusion, nausea and lethargy as compared to general anesthesia.
Peripheral Nerve Blocks are more relevant to the TKA and UKA procedures. A single dose femoral nerve block (addresses sensation to the anterior knee), and a single dose tibial nerve block (addresses sensation to posterior knee), and an adductor canal catheter block (provides anterior knee analgesia without impairing quad muscle strength, which is seen with femoral nerve catheters, which can slow physical therapy and risk patient falls). Adductor block seems to provide pain relief without significantly affecting function. Similarly, patients previously received single dose sciatic blocks, however, due to reports of postoperative falls, the tibial block reduces the side effect of muscle weakness.     
Patients receive a peri-articular injection (also known as local infiltration analgesia).
Peri-articular injections (PAI). There are a number of cocktails that surgeons have developed. Many include morphine, epinephrine (to increase longevity), ketorolac, depomedrol, bupivacaine, lidocaine, etc. Other surgeons use the slow-release bupivacaine (liposomal bupivacaine suspension called Exparel®, Pacira). Multiple studies have failed shown significant benefit of liposomal bupivacaine over the “homemade” cocktails combining bupivacaine, epinephrine and other medications. Nonetheless, all of the periarticular injections have demonstrated significantly positive effect on patient outcomes.
One RCT blinded patients to PCA (epidural) vs. PAI and showed higher oral opioid use and pain scores in the PAI group, although PCA group had higher opioid related adverse events like nausea/vomiting. Study suggests PAI has limitations. 
Results from RCT suggest patients with periarticular injections report better pain control, decreased opioid use, improved physical therapy and lower complications from opioids such as nausea and vomiting. Its unclear whether injections shorten hospital stay, but clearly otherwise show significant benefits.
Multimodal regimens have been shown it reduce pain scores (VAS) and opioid use, although there does not appear to be a significant effect on early function. These regimens typically include a combination of the following: NSAIDs, short- and long-acting narcotics (i.e. oxycodone and oxycontin), IV acetaminophen, and IV dexamethasone, and pregabalin postoperatively.      
This broad class of drugs include short-acting oral medications (Percocet, Vicodin, Oxycodone, MsContin®, Dilaudid) and long-acting oral medications (OxyContin®, MsContin®), and IV medications (Dilaudid, Morphine, Fentanyl).
Mechanism: Opioids block the hand-off of "pain information" from the peripheral nerves to the spinal nerves at the dorsal horn of the spinal cord. The spinal nerves, brain stem, thalamus, and cerebral cortex comprise the ascending pain transmission system. The opioid receptors are found at the descending inhibitory system that affects spinal transmission of pain both at the pre and post-synaptic sites. There are at least 3 opioid receptors: Mu, Kappa, Delta.
PCA: Patient-Controlled Analgesia has been a popular form of pain control for many decades. It has been widely published in the literature as having favorable patient satisfaction and pain control. However, the use of PCA has been more recently associated with higher rates of opioid related adverse events such as nausea and vomiting, constipation. Further, the dosages given are short acting IV medication, and patients hit the button when they are already in pain. The goal of modern pain management is to prevent patients from repeating feeling pain stimuli and to provide long-term baseline coverage
historical note: There are news articles every month discussing the growing opioid epidemic in the United States. Here is a brief historical perspective. The price of prescription painkillers became inexpensive in the 1990s and rates of drug overdose have increased > 400% (1999 to 2011). Purdue Pharma introduced OxyContin® in 1996 and aggressively marketed the medication (at that time an unprecedented marketing strategy for a Schedule II opioid). The owners of Purdue Pharam were physicians - three brothers from New York. The New Yorker recently wrote a very interesting profile on the Sackler Family. In just 5 years, prescriptions increased 10-fold and drug sales were almost 90% of the company’s revenue. The company argued that its time-release formula was less addictive than Percocet or Vicodin, despite later findings to the contrary. In 2007 the US Dept of Justice fined the company $634.5 million for misleading the public about risks of OxyContin® addiction. The lasting result of this marketing campaign was the shift in how pain was understood by the American public. Pain was once something that was endured. Now its believed to be something that can be completely eliminated with a pill. Pain became unacceptable. In 2015, there were over 250,000,000 opioid pills prescribed, there were >30,000 overdoses, and an estimated 2.6 million people addicted to prescription pain killers. Over 75% of heroin users started with prescription opioids.
-celecoxib: Commonly started preop and continued postop. May be administered as 400 mg preop, then 200 mg BID 5 days post-op. The use of celecoxib has demonstrated improved pain scores for 72 hours, decreased morphine use 24 hours, no difference in functional outcomes. . A similar study looking at 81 TKA, 60 THA also found decreased opioid consumption and improved pain scores during hospitalization in the celecoxib group . The dose of celecoxib should be reduced in half with borderline renal failure and those older than 70 years old.
Mechanism: Prostaglandins (PGE1, 2) are not mediators of pain transmission but rather contribute to pain by sensitizing nociceptive nerve endings to stimuli (histamine, bradykinin). NSAIDS block COX enzymes, reduce prostaglandin production (either reversibly or irreversibly), and prevent nerve sensitization. Selective COX-2 inhibitors don’t interfere with hemostasis and therefore patients can continue to take medications until the day of surgery (COX-1 continues to produce prostacyclin allowing gastric mucosa protection and allowing platelet aggregation).
-ketorolac: Typical dosing is 30 mg IV every 6 hours. Onset is about 10 minutes, peak effect at 2 to 3 hours, and lasts about 6 to 8 hours. Caution in patients with renal insufficiency, and elderly patients with impaired creatinine clearance.
Mechanism: The only IV NSAID. Analgesic strength has been compared with opioids and 30 mg of ketorolacis equivalent to 12 mg of morphine .
IV Acetaminophen. The tradename is Ofirmev® (Mallinckrodt) is given 1000 mg IV Q8H often dosed 1-3 times on postop day #0. Should be held in patients with liver disorders. Many hospitals are limiting its use due to increased costs (a medication owned by a Private Equity group that increased the cost overnight from under $20 to over $40). 
Mechanism: Inhibits central prostaglandin synthesis without inhibiting peripheral prostaglandin synthesis (weak anti-inflammatory effect, doesn’t inhibit COX). It has no effect on platelet function or gastric mucosa.
Gabapentinoids (Gabapentin – Neurontin; Pregabalin – Lyrica).
Administered 150 mg preop, then 75 mg BID for 1 week post-op in conjunction with 200 mg Celebrex PO BID for 3 days.
In RCT, shown to decrease PCA morphine use 24 hours after surgery and decrease Percocet use 1 week after surgery with improved pain scores 1 week after surgery (no effect on pain or function at 6 weeks or 3 months) . However, a recent meta-analysis looking at 12 RCT comparing gabapentinoids vs. placebo for postoperative pain control found no clinically significant differences in pain at 24, 48, 72 hours. This study recognized a difference in pain scores, however this difference was not clinically significant, and furthermore there was no impact on knee range of motion, and furthermore it was associated with a significant increased risk of sedation. 
IV Dexamethasone: This is given as 1 or 2 doses on postop day# 0. Should be held in diabetics.   
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