Reimagining Pain Management: Pharmacists Urged to “Deconstruct the Cupcake”

“Not everybody has hypertension. Not everybody has hyperlipidemia. But everybody has pain,” said Lee A. Kral, PharmD, FASHP, CPE, CPMC, NBC-HWC, in a session at the American Society of Health-System Pharmacists (ASHP) Pharmacy Futures 2025 meeting in Charlotte, North Carolina, from June 7 to 11. Kral and her co-presenter, Emma Murter, PharmD, MPH, urged attendees to rethink their approach to pain management through a novel—and memorable—metaphor: the cupcake.¹

Image credit: Nemanja | stock.adobe.com

Pain management, Kral explained, is like a cupcake. Its base—the cake—represents functional or restorative therapy. The flavor is cognitive behavioral therapy, which shapes how patients interpret and manage their pain. Fillings symbolize interventional techniques to boost functionality, while frosting reflects first-line analgesics. Sprinkles, like opioids, are optional and sometimes unwanted toppings—never the base.¹

“Everybody likes a different cupcake,” Kral said. “Everybody has different pain, so we have to tailor [treatment] to that patient. And that’s the beauty of what we do as health care providers.”¹

What’s Not Working?

Kral stressed that the current pain management toolbox—nonsteroidal anti-inflammatory drugs (NSAIDs), physical therapy, opioids, and pain scales, among other tools—isn’t doing enough. Chronic pain affects approximately 24% of Americans, a percentage that has barely budged in decades.² Data have also shown increased chronic pain with age and disproportionate burden on American Indian, Alaska Native, and rural populations—groups that often lack access to multi-resource care.²

“It’s not getting better. It may actually be increasing in prevalence, and the high impact [pain] is still high, so apparently, what we’ve been doing doesn’t work,” Kral said. “So how do we do it differently?”¹

Pharmacists must be familiar with pain phenotypes in order to best guide therapy. These include nociceptive pain, which is tissue damage-driven, localized, and diagnosable. Neuropathic pain is also typically diagnosable and is caused by nerve damage. Nociplastic pain, however, is poorly localized, with altered nociception but no clear tissue or nerve damage.¹

“[Patients with nociplastic pain] still have pain… But if we can’t pinpoint it, that’s what makes us really uncomfortable,” Kral said.¹

Frosting First: The Role of Analgesics

Murter explained that medications such as NSAIDs, acetaminophen, neuropathic agents, antidepressants, muscle relaxants, and topicals form the “frosting” on the pain management cupcake. They’re essential, not optional.

NSAIDs are foundational for inflammatory pain. Long-term use may be appropriate for conditions like chronic low back pain. In individuals with hip and knee osteoarthritis in the SPACE trial, NSAIDs performed as well as opioids over 12 months.³

Acetaminophen works for non-inflammatory pain and boosts NSAID efficacy. However, Murter noted that chronic use requires caution due to hidden sources in other common OTC medications, as well as liver toxicity risks.¹

Finally, adjuvants such as gabapentinoids, antidepressants (particularly serotonin norepinephrine reuptake inhibitors [SNRIs]), muscle relaxants, and topicals offer synergistic effects and should be tailored by pain phenotype. Although compounded topicals can be expensive, the ability to personalize them can make them particularly effective and therefore, sometimes, worth the expense, Murter said.

Tramadol, meanwhile, presents an interesting conundrum. Its parent compound is an SNRI, and it has CYP2D6 metabolism before becoming 0-desmethyltramadol, which is an opioid. This raises the question of whether it should be used in chronic pain or neuropathic chronic pain.

“I try to think of tramadol as the funfetti of the cupcake world,” Murter said. “Is it frosting? Yes. Is it sprinkles? A little bit, yes. It’s definitely a tool that can be used; it can be helpful, but just know that it’s kind of got its foot in both worlds when it comes to frosting and sprinkles.”

Opioids, Like Sprinkles, Should Be Used Sparingly

Although opioids have a place in treatment—specifically short-term use in acute or neuropathic pain—Kral said they are not effective for chronic nociplastic pain and can actually make it worse. Studies have consistently shown minimal improvement in function or quality of life with long-term opioid use and increased adverse effects (AEs) and risks of discontinuation due to AEs.^4-6

“Sprinkles can make the world a happier place, but if you start throwing sprinkles on frosting, some of them bounce off and some of them start spreading to other cupcakes, and then you have a hot mess,” Kral said. “And isn’t that what happened with opioids?”

The Cake: Functional Therapy

Many studies have highlighted the benefits of functional therapy, such as physical therapy, yoga, and simple exercises. For instance, exercise was ranked as the most effective intervention for knee osteoarthritis in a study published in the Journal of Orthopaedic and Sports Physical Therapy, outperforming NSAIDs and opioids in network analyses.⁷ For acute low back pain, early physical therapy was found to improve pain scores at 1 to 3 months, but not at 12 months—likely due to natural recovery over time.⁸

Yoga, especially for lumbar disc herniation, showed significant improvement across pain, disability, and global assessment scores. For patients with diabetic neuropathy, even simple hand and foot exercises improved motor function, although there was no significant difference in sensory scores.^9,10

Filling the Gaps With Interventions

Procedures such as sympathetic nerve blocks, trigger point injections, and epidural steroid injections are “fillings” that temporarily restore function, perhaps enough for the patient to go to physical therapy. These options can be diagnostic and therapeutic, but caution is warranted, as they can also result in infection, nerve injury, or hematoma.

“A lot of pain clinics now are using anesthesia,” Kral said. “Can that patient who’s on propofol tell you if you got the needle in the wrong place? No. This is where nerve injury happens.”

Deconstructing the Cupcake: Beyond Medications

Perhaps the most meaningful message came with the call to “deconstruct the cupcake.” Chronic pain, the presenters emphasized, is a biopsychosocial-spiritual disorder. Creating patient-centered combinations of all of the available ingredients is crucial to addressing the problem. Crucially, pharmacists must educate patients about realistic expectations, especially for those with long-term, chronic pain that will likely never go away entirely.

“As a provider, as a patient, this is the toughest part. It doesn’t mean we can’t do it, it just takes a little more effort and time,” Murter said. “But what we want to do is remove the expectation that 12 years of pain are going to be removed in 12 days.”

Mindfulness practices, acceptance and commitment therapy, and a focus on lifestyle, maladaptive coping, and pain catastrophizing can all be vital tools pharmacists use to help patients regain control and improve their quality of life.

“These are things that pharmacists can incorporate into their practice—because I do,” Kral said.

Conclusion

Pharmacists, as accessible and trusted health care professionals, are in a prime position to apply this personalized, layered approach to pain management. By understanding the ingredients that make up each patient’s unique pain journey and all of the treatments that can go into the “cupcake,” pharmacists can offer more thoughtful, effective care and help turn the tide on chronic pain.

REFERENCES

1. Kral LA, Murter E. Chronic Pain Management: As Easy as Cupcakes. Presented at: American Society of Health-System Pharmacists Pharmacy Futures 2025. Charlotte, NC; June 8, 2025. Accessed June 8, 2025.

2. Lucas JW, Sohi I. Chronic pain and high-impact chronic pain in US adults, 2023. NCHS Data Brief, No. 518. Hyattsville, MD: National Center for Health Statistics. Accessed June 8, 2025. https://www.cdc.gov/nchs/products/databriefs/db518.htm

3. Krebs EE, Gravely A, Nugent S, et al. Effect of opioid vs nonopioid medications on pain-related function in patients with chronic back pain or hip or knee osteoarthritis pain: the SPACE randomized clinical trial. JAMA. 2018;319(9):872-882. doi:10.1001/jama.2018.0899

4. Osani MC, Lohmander LS, Bannuru RR. Is there any role for opioids in the management of knee and hip osteoarthritis? A systematic review and meta-analysis. Arthritis Care Res (Hoboken). 2021;73(10):1413-1424. doi:10.1002/acr.24363

5. Cashin AG, Wand BM, O’Connell NE, et al. Pharmacological treatments for low back pain in adults: an overview of Cochrane reviews. Cochrane Database Syst Rev. 2023;4(4):CD013815. doi:10.1002/14651858.CD013815.pub2

6. Sommer C, Klose P, Welsch P, Petzke F, Häuser W. Opioids for chronic non-cancer neuropathic pain: an updated systematic review and meta-analysis of efficacy, tolerability, and safety in randomized placebo-controlled studies of at least 4 weeks duration. Eur J Pain. 2020;24:3-18. doi:10.1002/ejp.1494

7. Thorlund JB, Simic M, Pihl K, et al. Similar effects of exercise therapy, nonsteroidal anti-inflammatory drugs, and opioids for knee osteoarthritis pain: a systematic review with network meta-analysis. J Orthop Sports Phys Ther. 2022;52(4):207-216. doi:10.2519/jospt.2022.10490

8. Mannion AF, Brox JI, Fairbank JCT. Comparison of spinal fusion and nonoperative treatment in patients with chronic low back pain: long-term follow-up of three randomized controlled trials. Spine J. 2013;13(11):1438-1448. doi:10.1016/j.spinee.2013.06.101

9. Yildirim P, Gultekin A. The effect of a stretch and strength-based yoga exercise program on patients with neuropathic pain due to lumbar disc herniation. Spine (Phila Pa 1976). 2022;47(10):711-719. doi:10.1097/BRS.00000000004316

10. Win MMTM, Fukai K, Nyunt HH, Linn KZ. Hand and foot exercises for diabetic peripheral neuropathy: a randomized controlled trial. Nurs Health Sci. 2020;22(2):416-426. doi:10.1111/nhs.12676