Efficacy of Co-Crystal of Tramadol-Celecoxib (CTC) in Patients with Acute Moderate-to-Severe Pain: A Pooled Analysis of Data from Two Phase 3 Randomized Clinical Trials.

BACKGROUND AND OBJECTIVES: New acute pain medications are needed that provide effective analgesia while minimizing side effects and opioid exposure. Clinical trials of co-crystal of tramadol-celecoxib (CTC) have demonstrated an improved benefit/risk profile versus tramadol or celecoxib alone. We pooled data from two phase 3 clinical trials to evaluate the efficacy of CTC 200 mg twice daily (BID) in acute moderate-to-severe pain. METHODS: Efficacy data were pooled from STARDOM1 [acute pain following oral surgery (NCT02982161)] and ESTEVE-SUSA-301 [acute pain following bunionectomy (NCT03108482)]. The primary efficacy outcome was sum of pain intensity difference from 0 to 48 h (SPID0-48). RESULTS: A total of 344 patients received CTC 200 mg BID, 342 received tramadol 50 or 100 mg four times a day, 181 received celecoxib 100 mg BID, and 172 received placebo. The least-squares mean difference in SPID0-48 was -21.8 (p = 0.002) for CTC versus tramadol and -72.8 (p < 0.001) for CTC versus placebo. A similar pattern of SPID0-48 was observed with CTC versus comparator whether patients had moderate or severe pain at baseline. Reduction in pain intensity was faster and reached mild intensity earlier with CTC versus comparators. Patients were significantly (p ≤ 0.005) less likely to receive rescue medication within 4 or 48 h with CTC compared with tramadol or placebo. CONCLUSIONS: This pooled analysis reinforces the efficacy profile of CTC versus tramadol and, given that CTC permits lower daily tramadol dosing and thereby reduces unnecessary opioid use, this highlights its improved benefit/risk profile and its potential for the management of moderate-to-severe pain.

Co-crystal of tramadol-celecoxib (CTC) for acute moderate-to-severe pain.

OBJECTIVE: This narrative review aims to provide a clinical perspective on the potential role of co-crystal of tramadol-celecoxib (CTC) in the management of acute moderate-to-severe pain by synthesizing the available preclinical and clinical data, with emphasis on phase 3 trials. METHODS: A non-systematic literature review was performed using a targeted PubMed search for articles published between January 1, 2000, and May 2, 2023; all publication types were permitted, and selected articles were limited to those published in English. Search results were manually reviewed to identify references based on their preclinical and clinical relevance to CTC and management of acute moderate-to-severe pain. RESULTS: The crystalline structure of CTC alters the physicochemical properties of tramadol and celecoxib, modifying their pharmacokinetics. If taken in a free combination, tramadol reduces absorption of celecoxib. Conversely, administration of CTC slows tramadol absorption and lowers its maximum plasma concentration, while increasing celecoxib plasma concentration through its enhanced release. In clinical studies across models of acute moderate-to-severe pain, CTC demonstrated an early onset of analgesia, with improved efficacy and lower rescue medication use, compared with either agent alone. CTC's safety profile was in line with that expected for the individual components; no additive effects were observed. CTC exhibited tramadol-sparing effects, with efficacy seen at lower daily/cumulative opioid doses vs. tramadol alone. CONCLUSIONS: Results from phase 3 trials suggest that the modified physicochemical properties of tramadol and celecoxib in CTC translate into an improved clinical benefit-risk profile, including fewer opioid-related adverse effects due to lower overall opioid dosing.

Advances in the Management of Acute Postsurgical Pain: A Review.

Despite the millions of surgeries performed every year around the world, postoperative pain remains prevalent and is often addressed with inadequate or suboptimal treatments. Chronic postsurgical pain is surprisingly prevalent, and its rate varies with the type of surgery, as well as with certain patient characteristics. Thus, better clinical training is needed as well as patient education. As pain can be caused by more than one mechanism, multimodal or balanced postsurgical analgesia is appropriate. Pharmacological agents such as opioid and nonopioid pain relievers, as well as adjuvants and nonpharmacologic approaches, can be combined to provide better and opioid-sparing pain relief. Many specialty societies have guidelines for postoperative pain management that emphasize multimodal postoperative analgesia. These guidelines are particularly helpful when dealing with special populations such as pregnant patients or infants and children. Pediatric pain control, in particular, can be challenging as patients may be unable to communicate their pain levels. A variety of validated assessment tools are available for diagnosis. Related to therapy, most guidelines agree on the fact that codeine should be used with extreme caution in pediatric patients as some may be "rapid metabolizers" and its use may be life-threatening. Prehabilitation is a preoperative approach that prepares patients in advance of elective surgery with conditioning exercises and other interventions to optimize their health. Prehabilitation may have aerobic, strength-training, nutritional, and counseling components. Logistical considerations and degree of patient adherence represent barriers to effective prehabilitation programs. Notwithstanding all this, acute postoperative pain represents a clinical challenge that has not yet been well addressed.

Postoperative Restrictive Opioid Protocols and Durable Changes in Opioid Prescribing and Chronic Opioid Use.

Importance: Changes in postsurgical opioid prescribing practices may help reduce chronic opioid use in surgical patients. Objective: To investigate whether postsurgical acute pain across different surgical subspecialties can be managed effectively after hospital discharge with an opioid supply of 3 or fewer days and whether this reduction in prescribed opioids is associated with reduced new, persistent opioid use. Design, Setting, and Participants: In this prospective cohort study with a case-control design, a restrictive opioid prescription protocol (ROPP) specifying an opioid supply of 3 or fewer days after discharge from surgery along with standardized patient education was implemented across all surgical services at a tertiary-care comprehensive cancer center. Participants were all patients who underwent surgery from August 1, 2018, to July 31, 2019. Main Outcomes and Measures: Main outcomes were the rate of compliance with the ROPP in each surgical service, the mean number of prescription days and refill requests, type of opioid prescribed, and rate of conversion to chronic opioid use determined via a state-run opioid prescription program. Postsurgical complications were also measured. Results: A total of 4068 patients (mean [SD] age, 61.0 [13.8] years; 2528 women [62.1%]) were included, with 2017 in the pre-ROPP group (August 1, 2018, to January 31, 2019) and 2051 in the post-ROPP group (February 1, 2019, to July 31, 2019). The rate of compliance with the protocol was 95%. After implementation of the ROPP, mean opioid prescription days decreased from a mean (SD) of 3.9 (4.5) days in the pre-ROPP group to 1.9 (3.6) days in the post-ROPP group (P < .001). The ROPP implementation led to a 45% decrease in prescribed opioids after surgery (mean [SD], 157.22 [338.06] mean morphine milligram equivalents [MME] before ROPP vs 83.54 [395.70] MME after ROPP; P < .001). Patients in the post-ROPP cohort requested fewer refills (367 of 2051 [17.9%] vs 422 of 2017 [20.9%] in the pre-ROPP cohort; P = .02). There was no statistically significant difference in surgical complications. The conversion rate to chronic opioid use decreased following ROPP implementation among both opioid-naive patients with cancer (11.3% [143 of 1267] to 4.5% [118 of 2645]; P < .001) and those without cancer (6.1% [19 of 310] to 2.7% [16 of 600]; P = .02). Conclusions and Relevance: In this cohort study, prescribing an opioid supply of 3 or fewer days to surgical patients after hospital discharge was feasible for most patients, led to a significant decrease in the number of opioids prescribed after surgery, and was associated with a significantly decreased conversion to long-term opioid use without concomitant increases in refill requests or significant compromises in surgical recovery.

Celecoxib-tramadol co-crystal in patients with moderate-to-severe pain following bunionectomy with osteotomy: A phase 3, randomized, double-blind, factorial, active- and placebo-controlled trial.

BACKGROUND: Celecoxib-tramadol co-crystal (CTC) is a first-in-class analgesic co-crystal of celecoxib and racemic tramadol with an improved pharmacologic profile, conferred by the co-crystal structure, compared with its active constituents administered alone/concomitantly. AIM: We evaluated CTC in moderate-to-severe acute postoperative pain. MATERIALS AND METHODS: This randomized, double-blind, factorial, active- and placebo-controlled phase 3 trial (NCT03108482) was conducted at 6 US clinical research centers. Adults with moderate-to-severe acute pain following bunionectomy with osteotomy were randomized to oral CTC (200 mg [112 mg celecoxib/88 mg rac-tramadol hydrochloride] every 12 h), tramadol (50 mg every 6 h), celecoxib (100 mg every 12 h), or placebo for 48 h. Patients, investigators, and personnel were blinded to assignment. The primary endpoint was the 0-48 h sum of pain intensity differences (SPID0-48) in all randomized patients. Pain intensity was assessed on a 0-10 numerical rating scale (NRS). Safety was analyzed in patients who received study medication. Funded by ESTEVE Pharmaceuticals. RESULTS: In 2017 (March to November), 1323 patients were screened and 637 randomized to CTC (n = 184), tramadol (n = 183), celecoxib (n = 181), or placebo (n = 89). Mean baseline NRS was 6.7 in all active groups. CTC had a significantly greater effect on SPID0-48 (least-squares mean: -139.1 [95% confidence interval: -151.8, -126.5]) than tramadol (-109.1 [-121.7, -96.4]; p < 0.001), celecoxib (-103.7 [-116.4, -91.0]; p < 0.001), or placebo (-74.6 [-92.5, -56.6]; p < 0.001). Total treatment-emergent adverse events (TEAEs) were 358 for CTC and 394 for tramadol. Drug-related TEAEs occurred in 37.7% patients in the CTC group, compared with 48.6% in the tramadol group. There were no serious TEAEs/deaths. CONCLUSION: CTC provided greater analgesia than comparable daily doses of tramadol and celecoxib, with similar tolerability to tramadol. CTC is approved in the United States.

American Society of Regional Anesthesia and Pain Medicine 2021 John J. Bonica Award Lecture.

I am as deeply inspired and humbled to receive this prestigious award, as I am profoundly indebted to the Bonica Award selection committee and the American Society of Regional Anesthesia and Pain Medicine Board of Directors for recognizing my contributions to the development, teaching, and practice of pain medicine in the tradition of Dr John J Bonica. I would also like to recognize my parents, Aura and Tito for providing me with the support and the environment to fulfill my professional goals. Moreover, the support that I have gotten from my team at the hospital, and the Chair of my Department, Dr Mark Lema needs to be underscored.

New Insights Into the Pharmacological Management of Postoperative Pain: A Narrative Review.

Postoperative pain is prevalent and often undertreated. There is a risk that untreated or suboptimally treated postoperative pain may transition into chronic postoperative pain, which can be challenging to treat. Clinical guidelines recommend the use of multimodal analgesia, including non-steroidal anti-inflammatory drugs (NSAIDs), acetaminophen, and, in some cases, opioids. NSAIDs are a broad class of drugs with different attributes such as cyclo-oxygenase (COX)-1 or COX-2 selectivity, onset of action, and analgesic potency. NSAIDs are associated with gastrointestinal and cardiovascular side effects and should be administered at the lowest effective dose for the shortest effective duration but can be effective in postoperative pain. The role of opioids in postoperative analgesia is long-standing but has recently come under scrutiny. Opioids are often used in multimodal analgesic combinations in such a way as to minimize the total consumption of opioids without sacrificing analgesic benefit. Special clinical considerations are required for surgical patients already on opioid regimens or with opioid use disorder. A particularly useful fixed-dose combination product for postoperative analgesia is dexketoprofen-tramadol, which confers safe and effective postoperative pain control and reduces the risk of persistent postoperative pain.

Prevalence of burnout and its relationship to health status and social support in more than 1000 subspecialty anesthesiologists.

BACKGROUND: Physician burnout may be at 'epidemic' proportions due to factors associated with modern healthcare practice and technology. Practice attributes vary appreciably among subspecialists. Understanding burnout incidence and its associated factors could illuminate potential causes and interventions. We evaluated burnFout, mental and physical health, and social support and coping skills in acute and chronic pain physicians and pediatric and cardiac anesthesiologists. METHODS: We administered the Maslach Burnout Inventory Human Services Survey (MBI-HSS), a two-item self-identified burnout measure, the Veterans RAND 12-item Health Survey and the Social Support and Personal Coping Survey to subspecialty society members practicing acute and chronic pain management, pediatric anesthesiology and cardiac anesthesiology. Multivariable regression analysis compared the groups, and adjusted burnout prevalence was compared with an all-physician and an employed general population sample. RESULTS: Among 1303 participants (response rates 21.6%-35.6% among the subspecialty groups), 43.4% met established burnout criteria (range 30.0%-62.3%). Chronic pain physicians had significantly worse scores (unadjusted) than the other three groups of subspecialty anesthesiologists, the all-physician comparator group and the general population comparator group. Mental health inversely correlated with emotional exhaustion and depersonalization in all groups. Self-identified burnout correlated with the full MBI-HSS (R=0.54; positive predictive value of 0.939 (0.917, 0.955)). Physicians' scores for personal accomplishment were higher than population norms. CONCLUSIONS: This study provides data on burnout prevalence and associated demographic, health and social factors in subspecialist anesthesiologists. Chronic pain anesthesiologists had significantly greater burnout than the other groups. The self-identified burnout metric performed well and may be an attractive alternative to the full MBI-HSS.

Attitudes Towards and Management of Opioid-induced Hyperalgesia: A Survey of Chronic Pain Practitioners.

OBJECTIVES: Opioid-induced hyperalgesia (OIH) is a phenomenon whereby opioids increase patients' pain sensitivity, complicating their use in analgesia. We explored practitioners' attitudes towards, and knowledge concerning diagnosis, risk factors, and treatment of OIH. MATERIALS AND METHODS: We administered an 18-item cross-sectional survey to 850 clinicians that managed chronic pain with opioid therapy. RESULTS: The survey response rate was 37% (318/850). Most respondents (240/318, 76%) reported they had observed patients with OIH in their practice, of which 38% (84/222) reported OIH affected >5% of their chronic pain patients. The majority (133/222, 60%) indicated that OIH could result from any dose of opioid therapy. The most commonly endorsed chronic pain conditions associated with the development of OIH were fibromyalgia (109/216, 51%) and low back pain (91/216, 42%), while 42% (91/216) indicated that no individual chronic pain condition was associated with greater risk of OIH. The most commonly endorsed opioids associated with the development of OIH were oxycodone (94/216, 44%), fentanyl (86/216, 40%), and morphine (84/216, 39%); 27% (59/216) endorsed that no specific opioid was more likely to result in OIH. Respondents commonly managed OIH by opioid dose reduction (147/216, 68%), administering a nonopioid adjuvant (133/216, 62%), or discontinuing opioids (95/216, 44%). DISCUSSION: Most clinicians agreed that OIH is a complication of opioid therapy, but were divided regarding the prevalence of OIH, etiological factors, and optimal management.

The European Society of Regional Anaesthesia and Pain Therapy/American Society of Regional Anesthesia and Pain Medicine Recommendations on Local Anesthetics and Adjuvants Dosage in Pediatric Regional Anesthesia.

BACKGROUND AND OBJECTIVES: Dosage of local anesthetics (LAs) used for regional anesthesia in children is not well determined. In order to evaluate and come to a consensus regarding some of these controversial topics, The European Society of Regional Anaesthesia and Pain Therapy (ESRA) and the American Society of Regional Anesthesia and Pain Medicine (ASRA) developed a Joint Committee Practice Advisory on Local Anesthetics and Adjuvants Dosage in Pediatric Regional Anesthesia. METHODS: Representatives from both ASRA and ESRA composed the joint committee practice advisory. Evidence-based recommendations were based on a systematic search of the literature. In cases where no literature was available, expert opinion was elicited. RESULTS: Spinal anesthesia with bupivacaine can be performed with a dose of 1 mg/kg for newborn and/or infant and a dose of 0.5 mg/kg in older children (>1 year of age). Tetracaine 0.5% is recommended for spinal anesthesia (dose, 0.07-0.13 mL/kg). Ultrasound-guided upper-extremity peripheral nerve blocks (eg, axillary, infraclavicular, interscalene, supraclavicular) in children can be performed successfully and safely using a recommended LA dose of bupivacaine or ropivacaine of 0.5 to 1.5 mg/kg. Dexmedetomidine can be used as an adjunct to prolong the duration of peripheral nerve blocks in children. CONCLUSIONS: High-level evidence is not yet available to guide dosage of LA used in regional blocks in children. The ASRA/ESRA recommendations intend to provide guidance in order to reduce the large variability of LA dosage currently observed in clinical practice.

Ultrarestrictive Opioid Prescription Protocol for Pain Management After Gynecologic and Abdominal Surgery.

Importance: Opioids are routinely prescribed for postoperative home pain management for most patients in the United States, with limited evidence of the amount needed to be dispensed. Opioid-based treatment often adversely affects recovery. Prescribed opioids increase the risk of chronic opioid use, abuse, and diversion and contribute to the current opioid epidemic. Objective: To evaluate whether after hospital discharge, postsurgical acute pain can be effectively managed with a markedly reduced number of opioid doses. Design, Setting, and Participants: In this case-control cohort study, an ultrarestrictive opioid prescription protocol (UROPP) was designed and implemented from June 26, 2017, through June 30, 2018, at a single tertiary-care comprehensive cancer center. All patients undergoing gynecologic oncology surgery were included. Patients undergoing ambulatory or minimally invasive surgery (laparoscopic or robotic approach) were not prescribed opioids at discharge unless they required more than 5 doses of oral or intravenous opioids while in the hospital. Patients who underwent a laparotomy were provided a 3-day opioid pain medication supply at discharge. Main Outcomes and Measures: Total number of opioid pain medications prescribed in the 60-day perioperative period, requests for opioid prescription refills, and postoperative pain scores and complications were evaluated. Factors associated with increased postoperative pain, preoperative and postoperative pain scores, inpatient status, prior opioid use, and all opioid prescriptions within the 60-day perioperative window were monitored among the case patients and compared with those from consecutive control patients treated at the center in the 12 months before the UROPP was implemented. Results: Patient demographics and procedure characteristics were not statistically different between the 2 cohorts of women (605 cases: mean [SD] age, 56.3 [14.5] years; 626 controls: mean [SD] age, 55.5 [13.9] years). The mean (SD) number of opioid tablets given at discharge after a laparotomy was 43.6 (17.0) before implementation of the UROPP and 12.1 (8.9) after implementation (P < .001). For patients who underwent laparoscopic or robotic surgery, the mean (SD) number of opioid tablets given at discharge was 38.4 (17.4) before implementation of the UROPP and 1.3 (3.7) after implementation (P < .001). After ambulatory surgery, the mean (SD) number of opioid tablets given at discharge was 13.9 (16.6) before implementation of the UROPP and 0.2 (2.1) after implementation (P < .001). The mean (SD) perioperative oral morphine equivalent dose was reduced to 64.3 (207.2) mg from 339.4 (674.4) mg the year prior for all opioid-naive patients (P < .001). The significant reduction in the number of dispensed opioids was not associated with an increase the number of refill requests (104 patients [16.6%] in the pre-UROPP group vs 100 patients [16.5%] in the post-UROPP group; P = .99), the mean (SD) postoperative visit pain scores (1.1 [2.2] for the post-UROPP group vs 1.4 [2.3] for pre-UROPP group; P = .06), or the number of complications (29 cases [4.8%] in the post-UROPP group vs 42 cases [6.7%] in the pre-UROPP group; P = .15). Conclusions and Relevance: Implementation of a UROPP was associated with a significant decrease in the overall amount of opioids prescribed to patients after gynecologic and abdominal surgery at the time of discharge for all patients, and for the entire perioperative time for opioid-naive patients without changes in pain scores, complications, or medication refill requests.

The topical 5% lidocaine medicated plaster in localized neuropathic pain: a reappraisal of the clinical evidence.

Topical 5% lidocaine medicated plasters represent a well-established first-line option for the treatment of peripheral localized neuropathic pain (LNP). This review provides an updated overview of the clinical evidence (randomized, controlled, and open-label clinical studies, real-life daily clinical practice, and case series). The 5% lidocaine medicated plaster effectively provides pain relief in postherpetic neuralgia, and data from a large open-label controlled study indicate that the 5% lidocaine medicated plaster is as effective as systemic pregabalin in postherpetic neuralgia and painful diabetic polyneuropathy but with an improved tolerability profile. Additionally, improved analgesia and fewer side effects were experienced by patients treated synchronously with the 5% lidocaine medicated plaster, further demonstrating the value of multimodal analgesia in LNP. The 5% lidocaine medicated plaster provides continued benefit after long-term (≤7 years) use and is also effective in various other LNP conditions. Minor application-site reactions are the most common adverse events associated with the 5% lidocaine medicated plaster; there is minimal risk of systemic adverse events and drug-drug interactions. Although further well-controlled studies are warranted, the 5% lidocaine medicated plaster is efficacious and safe in LNP and may have particular clinical benefit in elderly and/or medically compromised patients because of the low incidence of adverse events.

Management of Postoperative Pain: A Clinical Practice Guideline From the American Pain Society, the American Society of Regional Anesthesia and Pain Medicine, and the American Society of Anesthesiologists' Committee on Regional Anesthesia, Executive Committee, and Administrative Council.

UNLABELLED: Most patients who undergo surgical procedures experience acute postoperative pain, but evidence suggests that less than half report adequate postoperative pain relief. Many preoperative, intraoperative, and postoperative interventions and management strategies are available for reducing and managing postoperative pain. The American Pain Society, with input from the American Society of Anesthesiologists, commissioned an interdisciplinary expert panel to develop a clinical practice guideline to promote evidence-based, effective, and safer postoperative pain management in children and adults. The guideline was subsequently approved by the American Society for Regional Anesthesia. As part of the guideline development process, a systematic review was commissioned on various aspects related to various interventions and management strategies for postoperative pain. After a review of the evidence, the expert panel formulated recommendations that addressed various aspects of postoperative pain management, including preoperative education, perioperative pain management planning, use of different pharmacological and nonpharmacological modalities, organizational policies, and transition to outpatient care. The recommendations are based on the underlying premise that optimal management begins in the preoperative period with an assessment of the patient and development of a plan of care tailored to the individual and the surgical procedure involved. The panel found that evidence supports the use of multimodal regimens in many situations, although the exact components of effective multimodal care will vary depending on the patient, setting, and surgical procedure. Although these guidelines are based on a systematic review of the evidence on management of postoperative pain, the panel identified numerous research gaps. Of 32 recommendations, 4 were assessed as being supported by high-quality evidence, and 11 (in the areas of patient education and perioperative planning, patient assessment, organizational structures and policies, and transitioning to outpatient care) were made on the basis of low-quality evidence. PERSPECTIVE: This guideline, on the basis of a systematic review of the evidence on postoperative pain management, provides recommendations developed by a multidisciplinary expert panel. Safe and effective postoperative pain management should be on the basis of a plan of care tailored to the individual and the surgical procedure involved, and multimodal regimens are recommended in many situations.

Research Gaps in Practice Guidelines for Acute Postoperative Pain Management in Adults: Findings From a Review of the Evidence for an American Pain Society Clinical Practice Guideline.

UNLABELLED: Acute postoperative pain is a common clinical condition that, when poorly controlled, can result in a number of significant negative consequences. The American Pain Society commissioned an evidence-based guideline on the management of postoperative pain to promote evidence-based, safe, and effective perioperative pain management. An interdisciplinary panel developed 31 key questions and inclusion criteria to guide the evidence review. Investigators reviewed 6556 abstracts from multiple electronic databases up to November 2012, an updated evidence review to October 2014, and key references suggested by expert reviewers. More than 800 primary studies not included in a systematic review and 107 systematic reviews were included. Despite a large body of evidence, a number of critical research gaps were identified where only low-quality or insufficient evidence was found to help guide clinical practice recommendations. This report identifies evidence gaps including optimal methods and timing of perioperative patient education, nonpharmacological modalities, combinations of analgesic techniques, monitoring of patient response to treatment, techniques for neuraxial and regional analgesia, and organizational care delivery models. Recommendations to help guide the design of future perioperative studies are offered. PERSPECTIVE: Acute postoperative pain is a common clinical condition requiring an evidence-based, planned, and multimodal approach. Despite the plethora of published evidence, much of it is weak and key questions remain unanswered. Researchers are encouraged to work together to produce strong evidence to help guide clinical decisions in perioperative pain management.

A review of the literature on multiple factors involved in postoperative pain course and duration.

OBJECTIVE: To review the literature on the progression from acute to chronic postoperative pain, to evaluate the evidence for the risk of progressing to persistent postoperative and chronic pain, and to identify characteristics of pharmacologic treatments to best tailor therapy to an individual patient's pain profile. BACKGROUND: Pain is most commonly classified by duration (acute, chronic) and pathophysiology (nociceptive, neuropathic); however, these descriptors alone incompletely describe pain. Additionally, the transition between acute and chronic postoperative pain is not well understood. METHODS: We conducted a qualitative review and evaluation of the literature on postoperative pain with respect to the above objectives. RESULTS: Individualized pharmacologic treatments require a complete characterization of a patient's pain profile, in terms of frequency of pain over the course of a 24-hour day and over time thereafter, frequency and duration of pain flares, and presence of neuropathic pain. These considerations can help guide the choice of pharmacologic treatment to meet patient needs over a 24-hour day and over time after surgery. With respect to opioid analgesics, acute pain requires rapid onset of analgesia and the ability to titrate analgesia to the changing characteristics of pain over a short period. For these reasons, short-acting opioid analgesics have been preferred; however, there are opioid formulations with rapid onset and extended release for reduced dosing frequency. Although nociceptive pain can typically be controlled by titration of the dose of an opioid analgesic, neuropathic pain may respond better to the addition of an antineuropathic medication rather than to opioid dose escalation. CONCLUSION: Advances in individualized pharmacologic treatment for postoperative pain have resulted in better pain control. Moreover, the recognition of sub-acute pain as a new entity is important because many surgical patients will need therapy beyond the first 8 days after surgery. In this group of patients the diagnosis of a neuropathic pain component will be important so that appropriate multimodal therapy may be implemented.

Opioids for chronic pain: new evidence, new strategies, safe prescribing.

In the United States, the prevalence and burden of chronic pain is large and still growing. Older adults (aged ≥65 years) make up a large portion of the population with chronic pain, and their presentation, diagnosis, and treatment tends to be more complicated because of age-related physiological changes and comorbidities. Guidelines on treating patients with severe back pain recommend opioids as an option for those who do not find adequate pain relief from acetaminophen or nonsteroidal anti-inflammatory drugs (NSAIDs). For older adult patients at higher risk for NSAID-related adverse effects, such as those who have gastrointestinal or cardiovascular disease, diabetes mellitus, or who are taking low-dose aspirin, opioids are recommended instead. Opioids may also be an appropriate option for patients with neuropathic pain who have not achieved adequate analgesia from maximum doses of first- and second-line antineuropathic agents. Still, opioids are not appropriate for all patients; rather, a differential diagnosis, consideration of other comorbidities, and the potential for opioid-related adverse effects and substance abuse are required to confirm the value of opioid treatment for each individual. For nonresponders to opioid therapy, opioid rotation should be considered before discontinuation is pursued.