Total hip arthroplasty (THA) is one of the most common major surgical procedures, and efficacious and cost-effective interventions as well as improving health-related quality of life and functional status of patients12). However, despite these advantages, THA can be associated with significant postoperative pain. Postoperative pain after THA can adversely affect early postoperative patient recovery. Moreover, pain can negatively impact postoperative mobility, increasing the risk of venous thromboembolic disease, and also may impair rehabilitation. As a result, these consequences of pain can prolong patient recovery and can increase hospital length of stay and cost. Therefore, adequate postoperative pain management after THA should be emphasized to enhance patient well-being and to minimize the physiologic consequences of pain34).

The preemptive use of multimodal approach is the most important concept of pain management, and has been widely accepted as a gold standard approach of pain management following THA56) Preemptive means that initial pain management should be performed before surgical stimuli, and multimodal approach means that multi-drugs or multi-modalities with different mechanisms or sites should be applied to get synergetic effect. Using two concepts, it has been known to be effective for postoperative pain management, reduction of the opioid consumption, and early initiation of rehabilitation eventually.

Pain is an unpleasant feeling that is conveyed to the brain by sensory neurons. The discomfort signals actual or potential injury to the body. The pain pathways form a complex, dynamic, sensory, cognitive, and behavioral system that evolved to detect, integrate, and coordinate a protective response to incoming noxious stimuli that threatens tissue injury or organism survival7).

Nociceptors are the specialized sensory receptors responsible for the detection of noxious (unpleasant) stimuli, transforming the stimuli into electrical signals, which are then conducted to the central nervous system (CNS). They are the free nerve endings of primary afferent Aδ and C fibers. Distributed throughout the body (skin, viscera, muscles, joints, meninges), they can be stimulated by mechanical, thermal or chemical stimuli. Transmission is divided into two categories, fast and slow. A-delta fibers detect and transmit pain quickly. These fibers are relatively small (1-6 m), thinly myelinated neurons that can conduct at speeds of 6 to 30 m/sec. C fibers are small (<1.5 m) and unmyelinated, conducting pain at 0.5 to 2 m/sec8). Complex interactions occur in the dorsal horn between afferent neurons, interneurons and descending modulatory pathways. Sensory neuron cell bodies are located in the dorsal root ganglia (DRG). DRG neurons are classically pseudo unipolar; one process extends into the peripheral nerve and the other process extends centrally, transmitting information through the dorsal root into the spinal cord. Most sensory fibers project from the DRG through the dorsal root and into the dorsal root entry zone (DREZ). At the DREZ, most unmyelinated and small myelinated axons project laterally to enter. Lissauer tract9) fibers then extend vertically in this tract for several spinal segments before synapsing. There are two main pathways that carry nociceptive signals to higher centers in the brain. The spinothalamic tract: secondary afferent neurons decussate within a few segments of the level of entry into the spinal cord and ascend in the contralateral spinothalamic tract to nuclei within the thalamus. The spinothalamic tract transmits signals that are important for pain localization. The spinoreticular tract fibers also decussate and ascend the contralateral cord to reach the brainstem reticular formation, before projecting to the thalamus and hypothalamus. This pathway is involved in the emotional aspects of pain (Fig. 1).

Historically, osteoarthritis pain has been considered a nociceptive pain related to the degree of structural damage to the affected joint. Even though patients with osteoarthritis present structural anomalies, the severity of these changes is not always proportional to the degree of pain or disability. A significant proportion of these patients show signs of central sensitization, with pain modulation and processing altered at the CNS level. Central sensitization is defined as "an increased response of CNS neurons which inform of pain when faced with inputs coming from low threshold mechanoreceptors"10). One of the characteristics of central sensitization is that, once installed, it can persist in time despite the lack of new painful stimuli from the periphery. In clinical practice, it is not uncommon to find patients with osteoarthritis who show symptoms even after prosthetic substitution. It has been noted that patients suffering with osteoarthritis and a high degree of pain and low pain thresholds before surgery run a greater risk of continued pain after getting a prosthetic knee, which has been interpreted as an accurate reflection of central sensitization11).

The purpose of arthroplasty of hip joint is to restore painless hip joint and provide early functional recovery. The rehabilitation protocol after THA is mandatory to improve range of motion and strengthen the muscle power around hip joint. This should include preoperative education, post-acute rehabilitation, such as early ambulation with walking aids and muscle strengthening exercise, and balancing exercise11). The structured postacute rehabilitation should be provided by trained professionals with knowledge at proper timing after THA. And for the early application of acute rehabilitation, well-designed multimodal pain management is necessary11). Also, the preoperative education can influence patient's perception of postoperative pain, walking and whole rehabilitation program. Consequently preoperative education can promote early discharge and reduce the total amount of analgesics usage. So, the preoperative education should be provided for patients and their family before THA11). The content should include the overall surgical procedure and rehabilitation protocol, expected benefits of THA, postoperative pain level and pattern, and pain management methods. Usually verbal format or small group sessions and is accompanied by a booklet as an adjunct to the verbal presentation12).

For the pain management after THA, it is more important to give information about postoperative pain than information about pathoanatomy, biomedical model of anatomy, and biomechanics of the disease and THA12). Educational sessions which aim to enhance patient knowledge of pain science and pain processing by the nervous system may help patients experience less fear and anxiety, and ultimately help alleviate postoperative pain12)13). Increasing a patient's knowledge of pain science may alter their perception of threat and they may then experience less fear and anxiety. Additionally, the increased knowledge and understanding of pain science may help modulate the pain experience. The patients also felt less pain perhaps because they were less stressed and better prepared to cope with pain. Anxiety has been reported to increase sensitivity to pain and to reduce anxiety decrease14).

Cryotherapy involves the application of bag of ice or cooled water to the skin surrounding injury and operation area, and has been traditionally used in the post-operative recovery. The cold penetrates the soft tissues and, when applied over a joint, decrease in tissue metabolism associated with a reduction in enzymatic activity, and preventing tissue damage caused by injury1516). Cryotherapy can reduce leukocyte migration and slow down nerve signal transmission, providing a reduction of inflammation and producing a short-term analgesic effect. Local hypothermia induces vasoconstriction and reduces extravasation of blood into surroundings tissues, local inflammation and edema production1718). Many studies examining the benefits of cryotherapy on recovery after TKA have shown a reduction in blood loss192021).

However, the clinical benefits on pain and range of motion have been equivocal, with some studies showing a benefit192021)2223) and others showing no difference in the treatment group192425). Because most of the studies includes limited number of subjects and are nonrandomised, unblinded, cohort studies, and there are scanty of studies about the hip arthroplasty, further evaluation about the benefit of cryotherapy is needed.

Multimodal analgesia strategy combines analgesics with different mechanisms of action to improve postoperative pain management. This approach targets the various pathways and neurotransmitters involved in nociception and may allow a reduction in the dose of each individual analgesic. By using non-opioid adjuncts, perioperative opioid requirements and opioid-related side effects can be reduced such as nausea, vomiting, sedation, respiratory depression, urinary retention, and constipation26). In this section, we review the following multimodal analgesic adjuncts: acetaminophen, nonsteroidal anti-inflammatory drugs (NSAIDs), selective cyclo-oxygenase-2 (COX-2) inhibitors, and gabapentinoid.

Patient controlled analgesia (PCA) is a delivery system, based on the use of a sophisticated microprocessor-controlled infusion pump, with which patients self-administer small, predetermined dose of analgesic medication to relieve their pain. PCA was developed in the early 1980s5253). Since its introduction, it has become widely used for the management of postoperative pain in major orthopedic surgery. Basic composition of PCA models include initial loading dose, bolus (demand) dose, lockout interval, and background infusion rate. The initial loading dose is titrated to achieve a minimal level of analgesia in the recovery room until the VAPS is ≤4. The bolus (demand) dose is the small amount of analgesia the patient receives each time. Optimal efficacy and safety of the analgesia depends on balance between the dose small enough to minimize adverse effect and the dose large enough to achieve analgesic satisfaction. The lockout period is defined as the length of time during which there will be no drug delivery. The lockout period is generally recommended between 5 and 10 minutes regardless of the opioid used. The background infusion rate is a constant rate of infusion administered to deliver the equivalent of the usual opioid dose, but it may cause respiratory depression.

Baseline characteristics of common opioids for PCA are summarized in Table 1. The common adverse effects of PCA include nausea and vomiting, pruritus, respiratory depression, sedation and confusion, and urinary retention. In recent decades, alternative routes of PCA have extensively been developed, although the intravenous (IV) PCA is the most widely used method of PCA delivery. Variable modalities of PCA such as peripheral regional, intranasal, and transdermal PCA have been introduced54). The characteristics of IV and epidural PCA, which is the two major delivery methods of PCA, are summarized in Table 2.

Epidural analgesia has been considered as one of the most effective methods for pain relief after surgery. Medical route of epidural blockage is directed to the epidural space of the spinal cord. Comparing to spinal block, a large dose of drug is typically necessary and the onset of analgesia is slower with epidural analgesia than with spinal anesthesia41). Contraindication of epidural block is uncorrected hypovolemia, increased intracranial pressure, coagulopathy, and prior spinal surgery. Adverse events include tachycardia, high blood pressure, light headache, metallic taste in mouth, ring in ears, and facial numbness.

Intraoperative periarticular injection of multimodal drugs is one of the most important procedures in multimodal pain control protocol115556). Injection using opioid and local anesthetics into injured or stretched nerves or tissues under the guidance of a surgeon can block axonal sodium channels and inhibit the conduction of pain messages. Wound infiltration with local anesthetic can act locally to reduce peripheral nociception with few systemic adverse effects385657). Several authors reported its effectiveness on reducing postoperative pain and improving postoperative mobility after THA115558596061). However, there is disagreement of the proper dosage and composition of injection drugs and techniques of injection and its efficacy on reduced opioid consumption is also unclear5661). The most commonly used drugs for periarticular injections include local anesthetics (bupivacaine and ropivacaine), ketorolac, morphine, clonidine, and steroids (Table 3). These components can activate directly the mu-opioid receptor near the surgical site inhibiting the local inflammatory response and relieving the pain by preventing the production of pain transmitters61). Steroids are effective for lengthening the duration of action of the periarticular injection but care should be taken using in patients with high risk of infection, such as diabetes or immunocompromised patients1156). Additional drugs can be used to prolong the effect (epinephrine) and to reduce the risk of infection (antibiotics). Authors also use periarticular injection as a part of multimodal pain control protocal since 200662). Components of authors' protocol are summarized in Table 4.

Although patient education and rehabilitation protocols are important in facilitating a patient's recovery after total joint arthroplasty, it cannot be overemphasized that the focus of rehabilitation protocol after joint replacement should be in controlling perioperative pain. Multimodal pain management has become an important part of the perioperative care of patients undergoing total joint arthroplasty. The principle of multimodal therapy is to use different techniques that target several different steps of the pain pathway, allowing more effective pain control with fewer side effects.