July 2026 in Pain Management: 10 Developments That Advanced and Challenged Patient Care

July 2026 brought meaningful developments across acute and chronic pain management, including the first OTC fixed-dose combination of acetaminophen and naproxen sodium, positive phase 2b findings for a selective NaV1.8 inhibitor, and FDA clearance of an investigational extended-release formulation of nefopam. New research also clarified opioid-use patterns following acute pain, evaluated patient-centered tapering for long-term opioid therapy, and expanded the evidence supporting multimodal treatment in procedural and cancer-related pain.

Other developments raised questions that pharmacists and other clinicians will need to address as the pain-management landscape evolves. Real-world data suggested that suzetrigine (Journavx; Vertex Pharmaceuticals) is already being prescribed outside its approved acute-pain indication, while genetic research strengthened the biological basis of fibromyalgia without yet producing an actionable diagnostic test or treatment.

Together, July’s developments reflected continued movement toward mechanism-based and individualized pain care, as well as persistent challenges involving medication safety, evidence translation, access, and opioid stewardship.

FDA Approves the First OTC Acetaminophen–Naproxen Combination

The FDA approved Tylenol with Naproxen, the first nonprescription fixed-dose product combining acetaminophen and naproxen sodium, for the temporary relief of minor aches and pains in adults and children aged 12 years and older. Each tablet contains acetaminophen 325 mg and naproxen sodium 110 mg. The labeled dose of 2 tablets delivers acetaminophen 650 mg and naproxen sodium 220 mg and may provide pain relief for up to 12 hours.¹

The product is indicated for pain associated with headache, backache, muscular aches, toothache, menstrual cramps, the common cold, and minor arthritis.¹ Combining analgesics with complementary mechanisms may provide longer-lasting relief while limiting the amount of either individual ingredient needed in a single dose; however, the availability of another combination analgesic also creates opportunities for unintentional therapeutic duplication.

Pharmacists will be essential for identifying concurrent acetaminophen- or nonsteroidal anti-inflammatory drug (NSAID)-containing products and counseling patients about acetaminophen-related hepatotoxicity and naproxen-associated gastrointestinal, cardiovascular, and renal risks. Other important considerations include alcohol consumption, anticoagulant or antiplatelet therapy, pregnancy, kidney or liver disease, and the use of other NSAIDs.¹

LTG-001 Produces Positive Phase 2b Results in Acute Postoperative Pain

LTG-001, an investigational selective inhibitor of the NaV1.8 sodium channel, significantly reduced moderate to severe acute pain following abdominoplasty in a randomized phase 2b trial involving 343 patients. Participants were randomly assigned to receive 1 of 3 LTG-001 dosing regimens, placebo, or an opioid comparator. All evaluated LTG-001 regimens significantly improved the time-weighted summed pain-intensity difference over 48 hours compared with placebo.²

NaV1.8 is expressed predominantly in peripheral sensory neurons and contributes to the transmission of pain signals. Selective inhibition of this channel could therefore reduce pain without directly engaging the central opioid pathways associated with respiratory depression, sedation, and dependence.² The study also produced encouraging opioid-sparing findings, supporting continued investigation of LTG-001 as part of the growing NaV1.8-targeted analgesic class.

The findings remain limited to a controlled postoperative model. Larger phase 3 trials will be needed to establish comparative effectiveness, safety, dosing, and consistency across different surgical procedures and acute-pain conditions.²

FDA Clears Phase 2 Development of Extended-Release Nefopam

The FDA cleared the investigational new drug application for MAX-001, permitting a randomized controlled phase 2 trial in acute postsurgical pain. MAX-001 is an extended-release oral formulation of nefopam, a centrally acting analgesic that is neither an opioid nor an NSAID.³ Although nefopam is used for pain management in several countries, it is not currently approved in the United States.

According to the developer, an earlier phase 1 trial demonstrated dose-proportional pharmacokinetics without serious or severe adverse events (AEs) or treatment-related discontinuations.³ Those preliminary findings supported advancement into phase 2 but do not yet establish clinical efficacy or safety in a broader surgical population.

The planned trial is expected to evaluate whether MAX-001 can provide effective oral analgesia while reducing reliance on opioids following surgery. If successful in later-stage development, it could be particularly relevant for patients who cannot receive NSAIDs or who face elevated opioid-related risks.³

Acute Pain Frequently Outlasts Opioid Use, but Some Patients Progress to Prolonged Treatment

A prospective cohort study of 1708 opioid-naive adults who were offered an opioid prescription for an acute-pain condition found that pain resolved after a median of approximately 20 days, whereas opioid use lasted a median of 7 days.⁴ Most participants therefore stopped using opioids before becoming completely pain-free, suggesting that opioids were primarily used during the most severe portion of the acute-pain episode.

However, approximately 10% of participants continued opioid use for at least 90 days. Patients recovering from surgery and those experiencing low back pain generally had longer pain trajectories than patients with several other acute-pain conditions.⁴ These findings reinforce the need to establish expectations regarding the anticipated course of pain, prescribe the lowest effective opioid dose and quantity, and reassess patients whose pain or opioid use continues longer than expected.

Medication disposal also emerged as a significant concern, with approximately 66.9% of participants reported having leftover opioids.⁴ Pharmacists can reduce the potential for diversion, accidental ingestion, and unsupervised reuse by providing secure-storage and disposal counseling when the prescription is dispensed. Because participants also used OTC analgesics and nonpharmacologic interventions, pharmacists should screen for duplicate acetaminophen or NSAID exposure and provide clear instructions for multimodal treatment.⁴

Real-World Suzetrigine Prescribing Extends Beyond Its Acute-Pain Indication

An analysis of electronic health record data from more than 3.6 million US adults prescribed suzetrigine or an opioid between February 2025 and April 2026 found that approximately 33.0% of suzetrigine prescriptions were associated with chronic pain encounters, compared with 6.7% of opioid prescriptions. Conversely, surgical encounters accounted for 10.2% of suzetrigine prescriptions and 48.8% of opioid prescriptions.⁵

Suzetrigine is FDA-approved for moderate to severe acute pain in adults. Its use for chronic pain is therefore off-label, and the analysis does not demonstrate that the medication is effective for chronic conditions. The observed pattern may partly reflect clinicians selecting suzetrigine for patients considered poor candidates for opioids. Nevertheless, the findings indicate that real-world use is already extending beyond the population and duration addressed by the approved indication.⁵

The analysis also identified substantial differences by specialty. Pain-medicine and orthopedic clinicians accounted for approximately 40.9% of suzetrigine prescribing but only 3.5% of opioid prescribing. Emergency medicine and general surgery accounted for 20.8% of suzetrigine prescriptions compared with 64.1% of opioid prescriptions.⁵ Pharmacists should verify the intended indication and duration, assess drug interactions and treatment response, and clearly distinguish emerging prescribing practices from uses supported by regulatory approval and prospective clinical evidence.

Patient-Centered Opioid Tapering Reduces Doses Without Worsening Pain

A randomized clinical trial published in July evaluated 3 voluntary opioid-tapering strategies among nearly 600 adults with chronic pain who were receiving long-term prescription opioids at 11 US clinical sites. All participants received individualized tapering, close clinical monitoring, and electronic support. The 3 groups received tapering alone, tapering plus cognitive behavioral therapy for chronic pain, or tapering plus a chronic-pain self-management program.⁶

At 1 year, the taper-only group met the study’s predefined criteria for tapering success, with participants reducing their opioid doses by approximately 50% without experiencing worsening pain. Adding cognitive behavioral therapy or the self-management program did not improve the primary tapering outcome. However, post hoc findings suggested that cognitive behavioral therapy may help reduce opioid-withdrawal symptoms during the tapering process.⁶

The findings support gradual, collaborative tapering among patients who want to reduce long-term opioid therapy. They should not be interpreted as support for abrupt discontinuation, rapid dose reduction, or involuntary tapering. Pharmacists can assist by reviewing dosage formulations, identifying drug interactions, monitoring withdrawal and pain symptoms, and helping clinicians develop feasible dose-reduction schedules.⁶

Intra-Arterial Dexamethasone Reduces Pain After Uterine Fibroid Embolization

A randomized clinical trial involving 40 women found that intra-arterial dexamethasone administered during uterine fibroid embolization reduced postprocedural pain compared with placebo. Average pain scores were 2.63 in the dexamethasone group and 4.28 in the control group, corresponding to a mean difference of −1.64 points.⁷

Pain after uterine fibroid embolization can be substantial and may require opioids, anti-inflammatory medications, and extended observation. Incorporating dexamethasone into the procedure could provide another component of multimodal analgesia while potentially reducing the need for rescue medication.⁷

The small study population limits the generalizability of the findings, and larger trials will be needed to confirm the magnitude and duration of benefit, identify appropriate patients, and evaluate uncommon AEs. Nevertheless, the results suggest that targeted intra-arterial administration may improve early recovery without compromising procedural effectiveness.⁷

Nonopioid Adjuvants Demonstrate Benefits in Chronic Cancer Pain

A Bayesian network meta-analysis published in July evaluated 23 randomized controlled trials involving 1845 patients with chronic cancer pain. NSAIDs and anticonvulsants demonstrated the strongest overall analgesic effects, and the combination of anticonvulsants with antidepressants had the highest probability of efficacy in the treatment rankings. Gabapentinoids and ketamine were also associated with opioid-sparing effects, including reductions in morphine-equivalent daily doses.⁸

The findings support incorporating appropriately selected nonopioid adjuvants into multimodal cancer-pain regimens rather than relying exclusively on opioid escalation. However, network meta-analyses frequently include heterogeneous populations, interventions, and outcome measures. Their treatment rankings should inform—not replace—individualized clinical judgment.⁸

Treatment selection should account for whether pain is nociceptive, neuropathic, inflammatory, or mixed, as well as kidney and liver function, gastrointestinal and cardiovascular risk, sedation, falls, drug interactions, and the patient’s cancer treatment. Pharmacists can help determine whether an adjuvant is appropriate and monitor whether opioid-sparing efforts preserve adequate analgesia and function.⁸

Largest Genetic Study of Fibromyalgia Supports Central Nervous System Basis

The largest genetic study of fibromyalgia to date analyzed data from 2,563,755 individuals, including 54,629 patients with fibromyalgia, and identified 26 independent genomic loci associated with the condition. The findings were published on July 28 in Nature Medicine.⁹

Fibromyalgia heritability was enriched in the brain and neuronal cell types, supporting the involvement of central nervous system pathways and central sensitization. The investigators also identified genetic overlap with low back pain, irritable bowel syndrome, posttraumatic stress disorder, anxiety, and depression, potentially helping to explain why these conditions frequently occur together.⁹

The strongest association was located within the HTT gene, while another signal implicated GPR52, a receptor involved in regulating huntingtin protein levels. The study did not establish that fibromyalgia is a form of Huntington disease, nor did it produce a diagnostic genetic test or immediately actionable treatment. Rather, it identified biological pathways that may inform future research and drug development.⁹

Investigators also found there were no substantial sex-specific genetic differences despite fibromyalgia being diagnosed considerably more often in women. This suggests that genetics alone may not explain the disparity, and that hormonal, environmental, social, or diagnostic factors may also contribute.⁹

Pediatric Analysis Finds No Clear Safety Difference Between Ibuprofen and Acetaminophen

A systematic review and meta-analysis published in July compared ibuprofen with acetaminophen for acute mild to moderate pain, with an emphasis on children and adolescents. The review included 15 studies and 2847 patients across postoperative, musculoskeletal, orthodontic, and emergency-care settings. Three studies involving 937 participants contributed to the primary meta-analysis of overall AEs.¹⁰

Ibuprofen was not associated with a statistically significant difference in the risk of any AE compared with acetaminophen, and the included studies reported no serious renal or hepatic AEs.¹⁰ However, the certainty of the evidence was limited, and follow-up periods ranged from single-dose assessments to 12 months.

The absence of a clear overall difference does not mean the medications are interchangeable for every patient. Selection should account for age, hydration, kidney and liver function, gastrointestinal or bleeding risk, asthma history, concomitant medications, and the anticipated treatment duration.¹⁰ Pharmacists should also counsel caregivers about weight-based pediatric dosing and the risk of unintentionally administering multiple products containing the same ingredient.

July’s developments demonstrated that pain management continues to evolve across drug development, clinical practice, and the understanding of chronic-pain biology. The emergence of new nonopioid candidates may eventually broaden treatment options for acute pain, but investigational therapies must still demonstrate consistent benefits and acceptable safety in larger trials. Meanwhile, evidence involving existing medications emphasizes that optimizing pain management requires more than replacing opioids with another drug.

For pharmacists, the month’s central lesson is the importance of matching therapy to the cause, severity, and anticipated duration of pain while continuously reassessing benefits and harms. This includes preventing duplication with OTC analgesics, monitoring off-label prescribing, supporting voluntary and individualized opioid tapering, identifying opportunities for multimodal treatment, and ensuring that efforts to improve medication safety do not result in inadequately treated pain.

REFERENCES

1. FDA approves first nonprescription fixed-dose combination of acetaminophen and naproxen sodium for 12-hour pain relief. FDA. News release. July 24, 2026. Accessed July 31, 2026. https://www.fda.gov/drugs/news-events-human-drugs/fda-approves-first-nonprescription-fixed-dose-combination-acetaminophen-and-naproxen-sodium-12-hour

2. Singla N, Katz NP, Vaughn B, et al. Phase 2b Trial of a NaV1.8 Inhibitor for Acute Pain. N Engl J Med. 2026;395(5):454-464. doi:10.1056/NEJMoa2602910

3. Maxona Pharmaceuticals receives FDA IND clearance for MAX-001 phase 2 acute pain clinical trial. PR Newswire. News release. July 15, 2026. Accessed July 31, 2026. https://www.prnewswire.com/news-releases/maxona-pharmaceuticals-receives-fda-ind-clearance-for-max-001-phase-2-acute-pain-clinical-trial-302826239.html

4. Jeffery MM, Bellolio F, Chang N, et al. Opioid Use and Pain Resolution for Acute Pain Among Opioid-Naive Patients. JAMA Netw Open. 2026;9(7):e2621875. doi:10.1001/jamanetworkopen.2026.21875

5. Suzetrigine prescribed often for chronic pain despite its acute-pain label. Epic Research. News release. July 14, 2026. Accessed July 31, 2026. https://www.epicresearch.org/articles/suzetrigine-prescribed-often-for-chronic-pain-despite-its-acute-pain-label/

6. Darnall BD, Perez L, Kao MC, et al. Patient-centered prescription opioid tapering methods: a randomized clinical trial. Ann Intern Med. Ann Intern Med. [Epub 7 July 2026]. doi:10.7326/ANNALS-25-04784

7. Briley K Jr, Reddy R, Cavada A, et al. Intraarterial Dexamethasone for Pain Relief After Uterine Fibroid Embolization: A Randomized Clinical Trial. JAMA Netw Open. 2026;9(7):e2625004. doi:10.1001/jamanetworkopen.2026.25004

8. Mercadante S, Vizzini G, Cascio AL. Comparative Efficacy of Non-opioid Analgesic Drugs for Chronic Cancer Pain: A Bayesian Network Meta-analysis. Drugs. Published online July 9, 2026. doi:10.1007/s40265-026-02356-4

9. Kerrebijn I, Bjornsdottir G, Arbabi K, et al. The genetic architecture of fibromyalgia across 2.5 million individuals. Nat Med (2026). doi:10.1038/s41591-026-04492-6

10. Marseglia GL, Marchisio PG, Milani GP, Miraglia Del Giudice M, Schiavetti I, Ciprandi G. Ibuprofen vs. acetaminophen for acute mild-to-moderate pain management: A systematic review and meta-analysis of safety with a focus on paediatric populations. Br J Clin Pharmacol. 2026; 1-11. doi:10.1002/bcp.70693