Why Does it Hurt so Much Part II: What can we do about it?!
In Part One, we explored the biochemistry of pain, including what pain is, how it works, and why it sometimes refuses to shut off. We saw how pain can shift from a helpful alarm system to a constant, overwhelming presence, especially in pain centric disorders like fibromyalgia and Ehlers-Danlos Syndromes (EDS).
Now comes the harder question:
What can we actually do about it?
The answer isn’t simple, and it isn’t one-size-fits-all. But there is good news! Research shows that multimodal care (layering medications, body-based therapies, mind-body approaches, and self-management) consistently works better than any single treatment on its own. This “toolkit approach” is now considered the gold standard in chronic pain care.
So let’s break down what actually helps, what doesn’t, and why.
⚠️ This blog is for educational purposes only. I am not a medical provider, and this is not medical advice. Please don’t make changes to your medications without consulting a qualified healthcare professional.
💊 Pharmacologic (Medication) Approaches
Medications are often the first tools offered, but most were designed for acute pain (like injuries and surgery), not the complex, long-term pain of EDS. Still, they can definitely be life savers when used carefully!
NSAIDs (Non-Steroidal Anti-Inflammatory Drugs)
Examples: ibuprofen (Advil, Motrin), naproxen (Aleve), celecoxib (Celebrex).
What it is: Widely used medications for pain, inflammation, and fever.
How it works: Block COX enzymes (cyclooxygenases), which are needed to produce prostaglandins, the chemical messengers that increase nerve sensitivity and inflammation. Fewer prostaglandins → less inflammation and less nociceptor activation.
Evidence/limits: Well-studied for arthritis, injuries, and short-term flares. Less effective for chronic, central pain.
⚠️Cautions: Long-term use can irritate the stomach, increase bleeding risk, and aggravate GI problems, POTS, or mast cell activation. Topical NSAIDs (e.g., diclofenac gel/Voltaren) may be safer for localized pain.
Acetaminophen (Paracetamol; Tylenol, Panadol)
What it is: A pain reliever and fever reducer.
How it works: Acts mainly in the brain and spinal cord to reduce perception of pain and regulate temperature. Unlike NSAIDs, it does not reduce tissue inflammation.
Evidence/limits: Useful for headaches, fevers, and mild aches. Less effective for connective tissue or inflammatory pain.
⚠️Cautions: Generally safe when used properly, but high doses can damage the liver.
Antidepressants (SNRIs and TCAs)
Examples: duloxetine (Cymbalta), amitriptyline (Elavil).
What it is: Originally developed for depression, but also used at low doses for chronic pain.
- SNRIs = Serotonin-Norepinephrine Reuptake Inhibitors.
- TCAs = Tricyclic Antidepressants.
How it works: Both increase serotonin and norepinephrine, which are neurotransmitters that influence how the spinal cord and brain process pain signals.
Evidence/limits: Effective for neuropathic pain, central sensitization, and fibromyalgia. Pain relief tends to plateau at lower doses; higher antidepressant doses often cause more side effects than benefit.
⚠️Cautions: Side effects include drowsiness, dry mouth, constipation, dizziness. Can interact with other medications.
Anticonvulsants (Anti-Seizure Medications)
Examples: gabapentin (Neurontin), pregabalin (Lyrica).
What it is: Medications developed for epilepsy, also widely used for nerve pain.
How it works: Bind to calcium channels in neurons, reducing excitability and calming abnormal nerve firing that causes burning, tingling, or “electric” pain.
Evidence/limits: Commonly prescribed for neuropathic pain and fibromyalgia. Some patients respond well; others notice little benefit.
⚠️Cautions: Side effects include fatigue, dizziness, swelling, and brain fog. Doses often need slow adjustment.
Muscle Relaxants (e.g., cyclobenzaprine/Flexeril)
What it is: Medications that act on the central nervous system to reduce muscle spasm and tension.
How it works: Decrease overactive motor neuron firing in the spinal cord. Cyclobenzaprine is structurally similar to tricyclic antidepressants and has additional sedative effects.
Evidence/limits: Helpful for acute muscle spasm and sometimes for flare management in EDS or fibromyalgia. Evidence for long-term use in chronic pain is limited.
⚠️Cautions: Common side effects include sedation, dry mouth, dizziness. Not recommended for daily, indefinite use due to tolerance and cognitive effects.
Low-Dose Naltrexone (LDN)
What it is: Naltrexone is normally used at high doses (50 mg) for opioid/alcohol dependence. At very low doses (0.1–6 mg), it appears to have different effects.
How it works: Calms glial cells (immune-like support cells in the nervous system), reducing neuroinflammation and resetting pain sensitivity.
Evidence/limits: Small studies and case reports suggest benefit in fibromyalgia and autoimmune conditions. There is promise for other pain conditions like EDS. At higher doses, it blocks opioid receptors and does not help pain.
⚠️Cautions: Generally well tolerated, but still considered experimental for chronic pain. May cause vivid dreams or headaches in some users.
Opioids
Examples: morphine, oxycodone, hydrocodone, fentanyl.
What it is: Potent painkillers that act directly on the brain’s opioid receptors.
How it works: Block pain signal transmission in the spinal cord and brain, while also releasing dopamine (reward/relief).
Evidence/limits: Extremely effective for acute pain (surgery, trauma, short-term crises). For chronic pain, effectiveness declines and risks rise. Opioids can also cause opioid-induced hyperalgesia making the nervous system even more sensitive to pain.
⚠️⚠️Cautions: High risk of dependence, tolerance, constipation, respiratory depression, and overdose. Most guidelines recommend avoiding long-term opioid use in EDS except under rare, closely monitored circumstances.
🧠 Neuromodulation
Neuromodulation means changing how the nervous system processes pain signals, rather than just targeting inflammation or tissue injury.
TENS (Transcutaneous Electrical Nerve Stimulation)
What it is: A small portable device with electrode pads that deliver mild electrical pulses through the skin.
How it works:
- The electrical pulses temporarily “jam” pain signals heading to the spinal cord.
- It also triggers release of endorphins (sometimes referred to as "natural painkillers").
Evidence/limits: TENs is safe, affordable, and available over the counter (aka, without a prescription). Some people find it very effective, while others don’t notice much change.
Vagus Nerve Stimulation (VNS)
What it is: The vagus nerve is one of the longest nerves in the body, running from the brainstem down through the neck, chest, and abdomen. It carries signals that regulate heart rate, digestion, immune activity, and the stress response. Stimulation can be done in three main ways:
- Implantable devices (surgically placed under the chest skin, with a wire around the neck vagus) deliver programmed electrical pulses. This is the “classic” medical VNS, and is FDA-approved for epilepsy and depression.
- Non-invasive devices (ear clips or handheld neck stimulators) deliver low-level stimulation through the skin, avoiding surgery. These are being tested for migraine, fibromyalgia, dysautonomia, and chronic pain.
- Lifestyle-based stimulation (deep slow breathing, cold water exposure, humming, yoga) gently activates the vagus nerve without equipment.
How it works:
- Lowers inflammation.
- Calms overactive stress responses.
- Improves autonomic balance (important in EDS, where dysautonomia is common).
Evidence/limits: Still emerging, but early trials and patient reports are promising. Access ranges from medical implants to simple daily practices.
Biofeedback
What it is: A technique that uses sensors to measure heart rate, breathing, muscle tension, or skin temperature, then displays the data in real time, allowing you to react to the feedback.
How it works: With practice, patients learn to regulate these biomarkers to lower stress and calm the nervous system.
Examples:
- Watching muscle tension on a screen and relaxing until it drops.
- Training heart rate variability (HRV), a measure of resilience.
Evidence/limits: The strongest support is for headaches and low back pain, but there's some promise for broader chronic pain. Biofeedback is usually delivered by trained therapists, though consumer devices and apps are rapidly emerging.
FSM (Frequency-Specific Microcurrent)
What it is: FSM delivers ultra-low electrical currents (far weaker than TENS, often not felt at all) that are tuned to tissue-specific “frequencies.” The idea is that different frequencies may resonate with particular tissues (like nerve vs. fascia vs. muscle) or conditions (like inflammation vs. scarring). These tiny currents interact with the body’s own electrical signaling to shift cellular activity toward healing rather than irritation.
How it works:
- Boosts ATP production (the cell’s energy molecule) by gently stimulating mitochondria (the cell's energy factory), which may help tissues repair micro-injuries and recover more efficiently.
- Lowers inflammatory messengers (like cytokines and prostaglandins), reducing the chemical “irritants” that keep nerves firing pain signals.
- May improve blood flow, which increases oxygen and nutrient delivery, helping calm irritated nerves and supporting healing.
Evidence/limits:
- Small studies and case series show benefits for chronic low back pain, post-exercise soreness, and as an adjunct to physical therapy.
- Patients often report rapid decreases in pain and stiffness, even when other treatments failed.
- ⚠️ Caveat: while anecdotal reports and small studies are very promising, large controlled trials are still lacking. The science is still catching up to the clinical enthusiasm.
Access:
- FSM is offered in some integrative pain clinics, including Cleveland Clinic.
- My friends at the Addison Sports Clinic) also offer FSM, with protocols tested extensively on EDS pain. Many of their patients report distinct improvements, highlighting its potential even if big trials are still pending.
- Home devices exist, but they require a prescription under the guidance of a provider .
👐 Body-Based Approaches
These are the foundation of EDS pain care, but only when they’re done gently and with providers who really understand hypermobility. The wrong approaches, such as aggressive stretching, high-impact workouts, and “no pain, no gain” PT, will cause more harm than good.
EDS-Informed Physical Therapy (PT)
What it is: A tailored PT approach designed for joint instability, poor proprioception, and muscle deconditioning, all common in EDS.
How it works:
- Improves proprioception (awareness of where your joints are in space), which is often impaired in EDS.
- Strengthens deep stabilizing muscles so they can act like “backup ligaments.”
- Focuses on slow, controlled motor learning rather than brute strength.
Evidence: Studies show proprioceptive training improves joint stability and reduces injury risk in hypermobility disorders.
Access/cautions: Needs an EDS-aware PT. Avoid “bootcamp” or “stretch it out” approaches which can make things worse.
Hydrotherapy (Aquatic Therapy)
What it is: Exercise performed in warm water to reduce joint stress while building strength.
How it works:
- Buoyancy reduces weight-bearing load on joints.
- Hydrostatic pressure provides gentle compression, aiding circulation and autonomic balance.
- Warmth relaxes muscles and reduces spasm.
Evidence: A 2023 meta-analysis (32 trials) found aquatic exercise significantly reduced pain and improved function in chronic musculoskeletal pain, sometimes more than land-based exercise.
Access/cautions: Widely available at rehab centers or community pools. Especially good for people who flare with land-based exercise.
Bracing, Splints & Compressive Supports
What it is: External supports for unstable joints, ranging from braces and splints to compressive garments and orthotics.
How it works:
- Mechanical support redistributes forces and limits painful ranges.
- Proprioceptive cueing from compression improves body awareness and stability.
Evidence: Reviews show bracing improves proprioception and reduces pain in knee instability; compression garments improve pain and balance in hEDS.
Access/cautions: Best used strategically (during activity or flares), not constantly, so muscles don’t weaken from disuse.
Heat and Cold Therapy
What it is: The simplest tools for pain relief, using thermal changes to modulate nerve activity and circulation.
How it works:
- Heat: Increases blood flow, reduces muscle spindle activity, eases stiffness, and provides competing sensory input (the “gate control” effect).
- Cold: Slows nerve conduction, reduces inflammatory signaling, and numbs acute pain.
Evidence: Reviews confirm both heat and cold are effective for short-term pain relief; human synovial studies show cold reduces inflammatory cytokines (IL-6, IL-1β).
Access/cautions: Safe, affordable, and easy to use at home. Use heat for chronic stiffness; cold for acute sharp flares. Contrast therapy (alternating hot/cold) may reduce soreness.
⚠️ Chiropractic Caution
What it is: High-velocity spinal manipulation.
Risks in EDS: Because ligaments and vessels are fragile, forceful manipulations can risk dislocations, vascular injury, or worsening instability.
Evidence: The Ehlers-Danlos Society specifically advises against high-velocity spinal/neck manipulations. Case reports describe vascular injury after manipulation.
Access/cautions: If used at all, only choose a provider trained in hypermobility, using low-force methods.
🧘♀️ Mind-Body Approaches
The brain and body are deeply interconnected. These approaches don’t deny the reality of pain, instead, they focus on how the nervous system interprets pain signals and how that interpretation can be shifted to reduce pain.
Cognitive Behavioral Therapy (CBT) for Pain
What it is: A structured form of talk therapy that teaches people to recognize and adjust unhelpful thought patterns and behaviors linked to pain.
How it works:
- Reduces “catastrophizing” (expecting the worst), which is strongly linked to higher pain intensity.
- Encourages pacing and problem-solving to avoid boom–bust activity cycles.
- Helps the brain interpret pain signals as less threatening.
Evidence: CBT is one of the most studied pain interventions. Multiple meta-analyses show it reduces pain distress, improves function, and enhances quality of life in chronic pain conditions.
Access/cautions: Usually delivered by psychologists or pain specialists and these days can be in-person or telehealth.
Acceptance & Commitment Therapy (ACT)
What it is: A modern form of therapy focused on acceptance of pain and commitment to living a meaningful life despite it.
How it works:
- Reduces the struggle against pain (which paradoxically worsens suffering).
- Builds resilience by focusing on values and actions that matter, even if pain remains.
Evidence: ACT has strong support for chronic pain, improving function and mood. Some studies suggest it may be as effective as CBT for reducing distress, with more focus on quality of life.
Access/cautions: Often provided by therapists trained in ACT, but digital apps are emerging.
Pain Neuroscience Education (PNE)
What it is: An educational approach that teaches people how pain works in the nervous system.
How it works:
- Explains concepts like central sensitization and neuroplasticity in plain language.
- Reduces fear and catastrophizing by showing pain ≠ damage.
- Shifts the brain’s “threat appraisal,” which lowers sensitivity over time. Evidence: Studies show PNE reduces pain, disability, and healthcare use when combined with movement-based therapies.
Access/cautions: Best delivered by PTs or clinicians trained in PNE. Needs reinforcement over time. **Note
Breathwork, Meditation, and HRV Training
What it is: Practices that target the autonomic nervous system, nudging the body out of chronic “fight-or-flight” mode.
How it works:
- Breathwork (slow diaphragmatic breathing) increases vagal activity, lowering heart rate and calming stress hormones.
- Meditation/mindfulness improves emotional regulation, reducing how much attention the brain gives to pain signals.
- HRV (Heart Rate Variability) training uses biofeedback to train more resilient autonomic balance, making pain less overwhelming.
Evidence: Meta-analyses show mindfulness and breathing reduce pain intensity and improve coping. HRV biofeedback is supported for headaches, fibromyalgia, and generalized chronic pain.
Access/cautions: Often self-directed, but effectiveness improves with coaching or structured programs. Tons of apps are emerging for this.
🔬 Emerging & Experimental Therapies
These are therapies that are being explored for chronic pain but are not yet widely proven. Some show great promise, others remain controversial.
Ketamine (oral, nasal, or IV)
What it is: A powerful anesthetic medication, used at much lower doses for chronic pain and depression.
How it works:
- Blocks NMDA receptors, interrupting the “wind-up,” or the process where repeated pain signals make the nervous system more sensitive over time.
- May “reset” central pain pathways, reducing central sensitization.
Evidence: Clinical studies show ketamine infusions can reduce severe neuropathic pain and fibromyalgia symptoms. Benefits are usually short-term, and maintenance protocols are still being studied.
Access/cautions: Only available in specialized clinics under medical supervision. Risks include dissociation, nausea, and blood pressure changes.
Regenerative Injections (PRP, Prolotherapy, Stem Cells)
What it is: Injections designed to stimulate tissue repair.
- PRP (Platelet-Rich Plasma): concentrated platelets from the patient’s blood, injected into damaged tissue.
- Prolotherapy: injection of an irritant (like dextrose) to stimulate healing.
- Stem cell therapies: experimental injections using stem cells to encourage regeneration.
How it works: By triggering a mild controlled inflammation, these treatments aim to strengthen ligaments and tendons that are too lax in EDS.
Evidence: Case reports and small studies suggest improvements in pain and joint stability, especially in hEDS, but data is limited and results vary.
Access/cautions: Offered in select sports medicine and regenerative clinics. Not FDA-approved for EDS; quality and safety depend heavily on provider expertise.
Note: A brand new study came out a few days ago on Prolotherapy. Keep a look out for my breakdown of that paper coming soon!
fMRI-Based Neurofeedback
What it is: A therapy where patients view real-time brain activity through fMRI (functional MRI) scans and learn to adjust it consciously. Essentially a more in depth version of Biofeedback.
How it works: Patients practice strategies to reduce activity in pain-related brain regions (like the insula or anterior cingulate cortex), retraining how the brain processes pain.
Evidence: Early trials show potential in chronic pain and depression, but the method is expensive, time-intensive, and still experimental.
Access/cautions: Available only in research settings or a handful of specialized clinics.
Suzetrigine (Journavx)
What it is: A new FDA-approved non-opioid pain medication (Just approved in 2025). Studies done for acute pain, unknown how it works on chronic pain.
How it works: Targets sodium channels involved in transmitting pain signals, without the risks of opioids.
Evidence: Clinical trials show it reduces chronic pain with fewer side effects than opioids. No EDS-specific data yet.
Access/cautions: Newly available; long-term outcomes and insurance coverage still being determined.
🧩 Why Pain Is So Hard to Treat in EDS
EDS pain is rarely just one thing. It’s a mix of:
- Tissue injury
- Nerve irritation
- Central sensitization
- Immune system involvement
- Hormonal influences That’s why a single pill or treatment rarely works. Pain in EDS is a system-wide process, not a single problem to “fix.”
✨ What Actually Helps
The most effective strategies are layered:
- Calm the overactive nervous system
- Support and stabilize joints
- Address inflammation and immune triggers
- Reframe pain as a process, not a punishment
- Build self-management and resilience The goal isn’t chasing a cure. It’s about turning the volume knob down so pain takes up less space in your life.
⚠️ This blog is for educational purposes only. I am not a medical provider, and this is not medical advice. Please don’t make changes to your medications without consulting a qualified healthcare professional.
📚 References & Further Reading
Gross L, et al. Contemopary Approaches to Multidisciplinary Pain Management. Neurol Clin. 2025;43(3):561-576. PMID: 40675666
Woolf CJ. Central sensitization: Implications for the diagnosis and treatment of pain. Pain. 2011;152(3 Suppl):S2–S15. PMID: 20961685
Chopra P, Tinkle B, et al. Pain management in Ehlers-Danlos syndromes. Am J Med Genet C Semin Med Genet. 2017;175(1):200–207. PMID: 28186390
Zhou Z, et al. # Management of chronic pain in Ehlers-Danlos syndrome: Two case reports and a review of literature. Medicine. 2018 Nov;97(45):e13115. PMID: 30407326
Nahin RL. Use of Multimodal Multidisciplinary Pain Management in the US. JAMA Netw Open. 2022;5(6):e2216765. PMID: 36342720
Song B, et al. Ehlers-Danlos Syndrome: An Analysis of the Current Treatment Options. Pain Physician. 2020;23(4):429-438. PMID: 32709178
Morcillo-Muñoz Y, et al. Multimodal Chronic Pain Therapy for Adults via Smartphone: Randomized Controlled Clinical Trial. J Orthop Surg Res. 2022 May 11;24(5):e36114. PMID: 35373776
Younger J, et al. The use of low-dose naltrexone (LDN) as a novel anti-inflammatory treatment for chronic pain. Clin Rheumatol. 2014 Feb 15;33(4):451–459. PMID: 24526250
Shi Y, Wu W. Multimodal non-invasive non-pharmacological therapies for chronic pain: mechanisms and progress. BMC Med 2023 Sep 29;21(1):372.PMID: 37775758
Shetty GM, et al. Effect of adjuvant frequency-specific microcurrents on pain and disability in patients treated with physical rehabilitation for neck and low back pain. J Bodywork Mov Ther. 2020 Oct;24(4):168-175 PMID: 33218507
Niesters, M., Martini, C., & Dahan, A. (2014). Ketamine for chronic pain: risks and benefits. Br J Clin Pharmacol, 77(2), 357–367. PMID: 23432384
Pereira, MG, et al. Effectiveness of Frequency-Specific Microcurrent (FSM) Therapy and Relaxation in Adults with Distress: A Pilot Randomized Controlled Trial. Healthcare 2025 May 15;13(10):1151.PMID: 40427987
Wang, T, et al. Efficacy of aquatic exercise in chronic musculoskeletal disorders: a systematic review and meta-analysis of randomized controlled trials. J Orthop Surg Res 2023 Dec 8;18:942 PMID: 38066577
Ho, T, et al. Best Practice Guidelines for Neuromodulation in Pain Management: Insight From the Neuromodulation Society of Australia and New Zealand Neuromodulation. 2025 May 27:S1094-7159(25)00145-X. PMID 40434331
Iannuccelli, C, et al. Fibromyalgia: one year in review 2025 Clin Exp Rheumatol. 2025 Jun;43(6):957-969. PMID: 40470564
Wang, J, Doan, L. Clinical pain management: Current practice and recent innovations in research Cell Rep Med. 2024 Oct 15;5(10):101786. PMID: 39383871
FDA press release on suzetrigine approval, January 30, 2025 Link
Cleveland Clinic FSM information. Link
Evidence-Based Clinical Guidelines
- American Academy of Pain Medicine Clinical Guidelines: Comprehensive and regularly updated recommendations for safe and effective pain diagnosis, treatment, and management, covering both pharmacologic and non-pharmacologic interventions. AAPM
- CDC Clinical Practice Guideline for Prescribing Opioids for Pain (2025): Current guidance for opioid prescribing, emphasizing alternative strategies and risk mitigation in chronic pain care.CDC
- ACOEM Chronic Pain Guideline (2024): Rigorous evidence synthesis and peer-reviewed recommendations on multidisciplinary approaches for chronic pain. ACOEM
- Northwest Pain Guidance Practice Guide: Practical tools and evidence-based strategies for clinicians treating chronic pain. NWPG
EDS and Chronic Pain Resources
- PM&R KnowledgeNow EDS Summary: Up-to-date clinical recommendations for physical medicine and rehabilitation of EDS. AAPMR
- EDS Society Pain Management Resources: Patient-friendly guides on pain management strategies tailored for EDS. EDS Society
- The Center for Complex Conditions: A leading multidisciplinary clinic renowned for its expertise in treating complex chronic pain and multisystem disorders, including Ehlers-Danlos Syndrome, fibromyalgia, POTS, and MCAS. Directed by Dr. Pradeep Chopra. Link
Fibromyalgia and Chronic Pain Reviews
- DVC Stem Fibromyalgia Treatment Review (2025): Updates on complementary therapies, SNRIs, and emerging interventions, including stem cell therapy for fibromyalgia. DVCSTEM
- MoreGoodDays Fibromyalgia Treatments 2024: Review of established and newer medications, including SNRIs, LDN, and cyclobenzaprine. MoreGoodDays
Research Reviews and Emerging Therapies
- FDA Draft Guidance on Non-Opioid Analgesics for Chronic Pain (2025): Resource for developers, but also clinicians tracking new non-opioid pain treatments. Federal Register
