Hope for Hypermobility: Part 2—An Integrative Approach to Treating Symptomatic Joint Hypermobility : Topics in Pain Management

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Hope for Hypermobility: Part 2—An Integrative Approach to Treating Symptomatic Joint Hypermobility

Daylor, Victoria BFA; Gensemer, Cortney PhD; Norris, Russell A. PhD; Bluestein, Linda MD

Author Information
Topics in Pain Management 38(9):p 1-10, April 2023. | DOI: 10.1097/01.TPM.0000933968.28098.59

Learning Objectives: After participating in this continuing professional development activity, the provider should be better able to:

  1. Describe the components of multimodal pain management for individuals with joint hypermobility.
  2. Examine the anticipated outcomes of specific treatment recommendations for improving pain, function, and quality of life for patients with symptomatic joint hypermobility.
  3. Explain the importance of sequence of treatments to determine which are effective for each patient.

This article is the second of 2 parts. In part 1, a general introduction was given to joint hypermobility with a discussion of the many types of pain associated with hypermobility syndromes. In part 2, the authors outline specific management according to a recently defined protocol.

Pain is one of the most common and debilitating symptoms of Ehlers-Danlos syndrome (EDS), a group of genetic connective tissue disorders that cause generalized joint hypermobility and tissue fragility. Building on part 1 of this series (March 2023, vol. 38, no. 8), the authors will outline treatment in this month's article.

Multimodal Pain Management for Hypermobility

One approach suggested by the authors is a multimodal one developed in a practice specializing in hypermobile patients. Through longitudinal work with hypermobile patients, one of the authors (L.B.) of this CE article developed a treatment method referred to as “MENS PMMS.” The acronym “MENS PMMS” stands for movement, education, nutrition, sleep, psychosocial, modalities, medications, and supplements, and was created after documenting the greatest degree of treatment success in those patients receiving a multimodal, comprehensive treatment approach (see Figure 1).

Figure 1.:
MENS PMMS treatment strategy for managing SJH.

Physical and psychological recovery, pain management breakthroughs, and the ability to lead more fruitful lives are possible for patients with symptomatic joint hypermobility (SJH) when approached in an all-encompassing fashion. A patient's care team can apply MENS PMMS by managing SJH through the guidelines outlined here.


Patients with SJH experience pain, fatigue, and frequent injury, which can create a barrier to or fear of physical activity.1–3 Continuing to move is paramount for patients with SJH to maintain and improve quality of life.4 Each patient has unique goals, whether to decrease pain or to dislocate less frequently. Those living with SJH should be working with knowledgeable practitioners willing to seek SJH education and work creatively to protect and increase stability of affected joints.4

In a review of exercise and rehabilitation studies of EDS, the results support the significant benefit for physical and psychological outcomes.5 Physical therapy (PT) and/or occupational therapy (OT) must be a priority in rehabilitation for SJH. Various aspects of SJH, such as extreme (dangerous) range of motion, joint instability, dizziness, and exercise intolerance, require a unique approach to PT, focusing on stability throughout the entire body. In addition, some patients may experience benefits from neurologic, orthopedic, or pelvic floor PT. Patients with altered voice, deep neck pains, choking, and swallowing problems may also benefit from voice therapy, which is a low-risk treatment option.6,7 Beyond PT/OT, patients may seek out alternative methods of exercise and movement depending on their tolerance. Gentle movement techniques that encourage efficient movement and well-being include Alexander technique, Feldenkrais, tai chi, and qigong. Those looking to incorporate posture and strength training into their exercise regimen could benefit from Pilates, Gyrotonic, and yoga. Additionally, active release technique can relieve tension and break up scar tissue. Each movement method listed may provide benefit to those with SJH, but will require trial and error to figure out which style suits the unique needs of the patient. It is important for the SJH patient population to maintain a safe range of motion when practicing movement modalities, and to seek out practitioners familiar with hypermobility.


Patient education is a useful tool to reinforce a treatment plan, including knowledge of the neuroscience of pain, placebo versus nocebo effect, catastrophization, kinesiophobia, and environmental modifications. Fortunately, pain neuroscience education for chronic musculoskeletal disorders is a proven method “in reducing pain and improving patient knowledge of pain, improving function and lowering disability, reducing psychosocial factors, enhancing movement, and minimizing health care utilization,” according to a systemic review.8

By understanding pain mechanisms, patients can improve their coping mechanisms, leading to the possibility of peace of mind. The placebo and nocebo effect can be described as a patient's prior positive or negative perception of their medical treatment. This field of study is continuing to be unveiled, but studies have demonstrated that those with anxiety are more likely to experience the nocebo effect when confronted with a change in treatment regimen.9 Contrastingly, those with a positive relationship and open communication with their physician show lessened symptoms of illness.10 To enhance treatment outcomes, the practitioner should introduce changes in procedure with positivity, optimism, and honesty.10 It is recommended to encourage placebo and prevent nocebo effects when possible. Pain catastrophization is the tendency to exacerbate the threat of the pain stimulus. Catastrophizing pain can have serious, negative effects on patient outcomes. In one study, a physical therapist provided preoperative patients (non-EDS) educational sessions on neuroscience of pain, showing meaningful decreases in pain catastrophization.11

Psychosocial, educational, and pharmacological interventions can be used to prevent catastrophization.8,11 Kinesiophobia, the fear of movement-related pain, is known to hinder treatment efficacy and prolong disability. Clinicians identifying kinesiophobia in initial stages of treatment can reduce the impact of fear and improve recovery.12–14 In one randomized control trial, Pilates was demonstrated to reduce pain and kinesiophobia in patients with chronic low back pain.15 Some comorbidities, such as mast cell activation disorder (MCAD), can have environmental and physical triggers.16 Triggers include extreme temperature, stress, foods, smoke, fragrances, xenobiotics, vibrations, pressure, and insect venom.16–18 By identifying known triggers and educating the patient on adaptive tools and lifestyle modifications, one can prevent and minimize future episodes. Educational resources for patients can be found in the form of books, audiobooks, podcasts, webinars, and classes, to find the best fit for each patient's learning style. Patient education in chronic pain and illness is especially important to provide coping strategies, help self-manage symptoms, prevent flare-ups, and empower patients to take control of their health.


Nutrition plays a key role in managing chronic illness, such that a poorly managed diet can contribute to musculoskeletal pain. Although research on SJH and nutrition is limited, nutritional intervention and dietary supplements may reduce symptoms and improve quality of life.19,20 Eating habits alter the chemical environment of the gastrointestinal tract and can affect degenerative diseases.21 This includes how we eat: for example, by sitting down and eating slowly, the parasympathetic nervous system activates, allowing proper absorption of nutrients.22 Gastrointestinal issues can be addressed with diet alterations such as soluble fiber to reduce diarrhea, low FODMAP (Fermentable Oligo-, Di-, Mono-saccharides, And Polyols) for irritable bowel syndrome symptoms, gluten-free to reduce abdominal discomfort even in individuals without celiac disease, and fiber supplementation to increase stool frequency.19,23,24 When treating MCAD, removing gluten, lactose, preservatives, additives, artificial sweetener, and alcohol (especially red wine, beer, and champagne) may minimize reactions.19,25,26 Additionally, those struggling with MCAD may wish to try a dietician-supervised elimination diet, which has demonstrated improvement in over 70% of cases.27 Recommended foods to avoid typically have high histamine levels, such as leftover foods, fermented foods, and canned fish.27,28 Recommended foods for patients with SJH include fresh produce (except tomatoes, citrus, eggplant, spinach, and strawberries); gluten-free whole grains; healthy fats; dairy (if tolerated); and fresh meat, poultry, or fish. When addressing nutrition, pro-inflammatory foods can contribute to chronic pain. Pro-inflammatory foods to limit include processed meat, eggs, sugar-sweetened beverages, refined grains, tomatoes, and nonoily fish.29 Anti-inflammatory foods to incorporate include leafy green vegetables, tea, coffee, fruit juice, dark yellow vegetables, and oily fish.29 Lastly, nutrient deficiencies should be identified in each patient and specifically targeted. Working with a registered dietician can be especially helpful for patients with gastrointestinal comorbidities.


Insufficient sleep plays a unique bidirectional role as both a cause and effect of pain, implying the significance in the role of quality sleep for those with SJH. Cognitive behavioral therapy for insomnia (CBT-I) has demonstrated promise in alleviating sleep disturbances and depression-related insomnia.30,31 CBT-I is a low-risk approach to promote natural sleep mechanisms through relaxation and the reduction of thoughts and behaviors that compromise sleep. CBT-I, access to natural light, and exposure to nature all may promote circadian rhythm and are ideal first-line approaches to improving sleep conditions.32

Sleep apnea is a known comorbidity of hypermobile-type EDS (hEDS), causing poor sleep and daytime fatigue.33–35 When addressing a patient's sleep issues, central and obstructive sleep apnea should be assessed for and treated.33,34 Additionally, those struggling with sleep should consider using weighted blankets and a supportive mattress and pillows.

Psychosocial Approach

When treating patients with chronic pain and disability, a psychosocial approach can be effective for versatile treatment. Trauma, anxiety, depression, and neurodivergence (eg, attention-deficit/hyperactivity disorder, autism spectrum disorder, dyslexia, and dysgraphia) can play roles in the underlying disorder and how the patient copes. Trauma can lead to chronic pain and a higher risk of persistent pain, and many SJH patients experience medically related trauma due to dismissal of symptoms by health care providers.36 Individuals with higher levels of baseline anxiety and depression are reported to have less surgical benefit (non-EDS joint replacement), increased pain, and poorer function years later.36–38 The transition from acute to chronic pain can even be predicted by psychosocial variables such as anxiety and depression.39 A recent study demonstrated that individuals with SJH have an odds ratio of 4.51 for meeting criteria of neurodivergence compared with the general population. They also demonstrated significantly more musculoskeletal pain and orthostatic intolerance in the neurodivergent group with the number of hypermobile joints mediating that the relationship.40

Different therapy methods can be beneficial in addressing the psychosocial factors of chronic illness. Eye movement desensitization and reprocessing is suggested to be effective in reducing chronic pain as supplementary treatment.41 Anecdotally, the dynamic neural retraining system has been helpful in practice, but research has yet to be published on verifying this method. Cognitive and dialectical behavioral therapy (CBT and DBT) show evidence of treatment for chronic pain reduction, anxiety, and pain catastrophization.42–44 Emotional awareness and expression therapy can effectively address the psychological factors of centralized pain.45,46 Anxiety is a common comorbidity, but differentiating the cause is an important aspect of well-rounded treatment. Anxiety produced by dysautonomia can differ from psychological anxiety, mimicking a hyperadrenergic response.47 Additional research is needed regarding anxiety and SJH comorbidities, but the psychosocial impact on pain and chronic illness are well established. This aspect of treatment should be taken into consideration to reduce magnified experiences with pain and to improve the ability to cope with complex medical conditions.


With no approved treatment or cure for hEDS or hypermobility spectrum disorder (HSD), patients with SJH often use various modalities to manage symptoms, whether self- or externally administered. There is little research on the effects of modalities used for HSD patients specifically. The following methods, in conjunction with other treatment, may offer holistic relief to patients with minimal risk.

Patients with SJH often use foot, finger, and/or oral orthosis (shoe inserts, finger splints, and bite splints). In a small clinical study of the use of finger orthosis for joint hypermobility, results suggested improved function and some evidence of minimized cognitive demand.48

Compressive clothing, abdominal binders, and sequential compression devices can be worn to provide support or increase circulation.49,50

Bracing can assist in retaining muscle tone and increase proprioception of affected joints.50

Research supports the use of vagus nerve stimulation to treat and prevent migraine51,52 This device can be used at home for multiple types of headaches.

The Scenar electrotherapy device is another noninvasive method to manage acute and chronic musculoskeletal pain. Current research of Scenar therapy shows contradictory findings, although some patients derived significant benefit.53,54

Transcutaneous electrical nerve stimulation devices can be used at home or in PT; although little evidence shows long-term benefit, it can provide immediate relief and improvement of functional disability.55,56

Scrambler therapy is a noninvasive, drug-free treatment with no reported side effects, used to treat chronic neuropathic pain, such as low back pain and neuropathies.57

Low-level laser therapy uses red or near-infrared light to relieve pain, reduce inflammation, and promote healing of chronic nonspecific low back pain, shoulder tendinopathy, and temporomandibular joint disorders.58–61

Fascial counterstrain therapy can be facilitated by a specialized physical therapist to treat multisystemic pain.62

Additional methods include massage therapy, kinesiology tapping, sauna, and Epsom salt baths. Patients may seek out dry needling, acupuncture, and/or acupressure treatments, for a vast array of symptoms related to pain and comorbidities of HSD.63–66

Interventional pain management procedures (eg, trigger point injections, epidural corticosteroid injections, peripheral nerve blocks, peripheral nerve stimulation, radiofrequency ablation, and spinal cord stimulation) may play either a diagnostic or therapeutic role.67

Regenerative medicine procedures are often offered to patients with SJH (eg, prolotherapy, platelet-rich plasma, and cell-based injections); however, data supporting efficacy are currently lacking and such therapies are not typically covered by insurance.

Patients with HSD urgently need treatment options and should consider holistic modalities with their clinicians after careful risk-benefit analysis.


There are several considerations when strategizing medications for this population. Pharmacogenomic testing can guide clinicians to tailor drug choices, doses, and frequency. Testing has become less expensive and should be considered for patients with complex, multisystemic conditions. Oral medications are more effective for widespread and/or nociplastic pain, whereas topical medications target specific areas. Medication compounding may help patients intolerant of excipients. Compounding pharmacies will often work directly with the patient to find a tolerable filler, capsule, and/or base. Insurance coverage may be more likely with documentation that the “patient is allergic to fillers in commercially available products.” Acidophilus filler and olive oil as a base for sublingual drops are often tolerated well, and gelatin capsules may be used as an alternative to cellulose.

Patients with SJH require a wide range of medications, in combinations unique to their symptoms and comorbid conditions. Medications that can be helpful in treating symptoms related to SJH include anti-inflammatory medications, muscle relaxants, opioids, benzodiazepines, cannabinoids, low-dose naltrexone, ketamine, tricyclic antidepressants, gabapentinoids, selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), and antihistamines.

Anti-inflammatory or neuro-anti-inflammatory medications may include acetylsalicylic acid, minocycline, acetazolamide, metformin, and pentoxifylline. Muscle relaxants should be considered as needed for dislocations and instability-related muscle spasms, while considering the possibility of increased instability when spasms compensate for ligament laxity. Benzodiazepines may help with MCAD in low doses.

Cannabinoids with cannabidiol and low doses of tetrahydrocannabinol can provide relief for pain, depression, anxiety, insomnia, and a wide range of other disorders.68 Evidence shows positive effects from “entourage effect” when terpenes are added to the cannabinoids.69

Naltrexone, an opioid antagonist, may be especially beneficial in low doses for centralized pain, a common feature of SJH. Low-dose naltrexone, via reduction of proinflammatory cytokines and suppression of glial cell activation, may act as a powerful analgesic via modulation of pain perception and sensitivity. Its immunomodulatory effects help with inflammatory and autoimmune conditions (which seem to occur in higher rates with SJH patients).

Research on the use of ketamine for chronic pain suggests efficacy in treating pain and related depression.70

Gabapentin or pregabalin effectively treat neuropathic pain conditions, which occur more frequently in those with SJH.71 SSRIs and tricyclic antidepressants can treat depression and chronic pain, with similar efficacies.72

SNRIs (norepinephrine), such as duloxetine, can target chronic pain (especially neuropathic pain) along with anxiety, although may exacerbate tachycardia in those with dysautonomia.

Opioids remain out of favor for chronic centralized pain; however, opioids may be beneficial short-term after acute injury (eg, dislocation) or painful procedures. Atypical opioids (tramadol, buprenorphine, and tapentadol) may be safer than conventional opioids (morphine, oxycodone, and fentanyl).73 SJH patients may be at higher-than-average risk for some opioid side effects due to their underlying condition(s) (eg, mast cell degranulation and bowel dysmotility). Respiration depression may be more frequent and/or severe especially in patients with sleep apnea, craniocervical instability (CCI), and/or cervicomedullary syndrome. Some patients with SJH may suffer from intractable pain (eg, due to adhesive arachnoiditis) where opioids may be an essential component of the palliative care regimen.

Special considerations are required for those with suspected or diagnosed MCAD, which, when left untreated, can contribute to peripheral and central sensitization. Excipients can be problematic, and it is suggested to avoid dyes, try different brands, and pill form (vs capsule) when possible. In some cases, children's formulations are necessary. Current treatments for MCADs include mast cell stabilizers, antihistamines, corticosteroids, leukotriene antagonists, monoclonal antibody injections (eg, omalizumab), and avoiding known food, drug, and environmental triggers.16,74–76 If MCAD contributes to a patient's fatigue, selecting a sedating antihistamine (one that crosses the blood-brain barrier) may paradoxically help with fatigue. Sedating H1 antihistamines include ketotifen, diphenhydramine, chlorphenamine, cyproheptadine, clemastine, doxepin, and hydroxyzine. Nonsedating H1 antihistamines in the United States include cetirizine, loratadine, fexofenadine, and levocetirizine. H2 antihistamines (eg, famotidine) are suggested in combination with an H1 antihistamine. Leukotriene antagonists can aid with respiratory symptoms, such as montelukast or zileuton for urgent relief.77,78 Cromolyn, a mast cell stabilizer, is another first-line medication for MCAD.79 Lastly, acetylsalicylic acid, a prostaglandin blocker, can reduce concurrent symptoms (pain, nausea, vomiting, etc) in those without a contraindication. Vaginal cromolyn or diphenhydramine can be used to treat MCAD-related menorrhagia and dysmenorrhea.80 Treating MCAD with SJH can be complex, but is essential to achieve optimal patient outcomes.

It is also of note that with complex symptoms, it can be difficult to isolate new symptoms that arise independently, as medication reactions, or medication interactions. This should be carefully examined and isolated, if possible.


Although data are lacking to establish effects of nutritional supplements on symptoms related to SJH, one can extrapolate from studies performed in cohorts with other painful conditions. Supplement use should be carefully supervised and specific to patients' symptoms and comorbidities. Whenever possible, foods should be used first to compensate for nutritional deficits.

Magnesium deficiency may contribute to fatigue, muscle spasms, poor sleep or memory, inflammation, anxiety, constipation, menstrual cramps, and migraines. Magnesium plays a crucial role in protein synthesis and in the proper functioning of the extracellular matrix. It is considered a “pivotal actor in tissue homeostasis.”81 Correcting magnesium deficiency may help alleviate some of the more bothersome symptoms related to SJH. Unfortunately, serum magnesium levels are not reflective of whole-body magnesium stores, because 99% of magnesium is found outside the extracellular fluid. Accurate laboratory testing is not yet available to determine total body human magnesium status.82

Vitamin D deficiencies correlate with chronic pain, delayed healing, and muscle fatigue, and when treated with vitamin D supplements, it has demonstrated benefit with chronic pain.83–85 Vitamin D deficiencies in SJH patients should be addressed, and are a low risk and cost-effective method of treatment.86 Vitamin C can aid in the body's repair of tissues, and benefit has been demonstrated to prevent the development of complex regional pain syndrome type I (CRPS-I) after wrist fracture and aid in complex wound healing for patients with EDS.87–89 Dosages should be monitored, to prevent kidney stones and hemochromatosis. Suggested B vitamins include B1, B2, and B12 for patients with dysautonomia, migraines, and an increased risk of deficiency (vegan or vegetarian), respectively. B12 deficiencies cause neurologic disorders, and using supplements has demonstrated reduction in chronic nonspecific low back pain.90

Fish oils are high in omega-3 fatty acids with anti-inflammatory properties. Fish oils such as docosahexaenoic acid (DHA) and eicosapentaenoic acid are currently used for chronic conditions such as rheumatoid arthritis.91,92 Studies have concluded that doses of polyunsaturated fatty acids at more than 2.7 g/day for over 3 months in patients with rheumatoid arthritis reduced their need for nonsteroidal anti-inflammatory drug (NSAID).93

Curcumin (a compound in turmeric) can be used to manage inflammation, arthritis, and anxiety, and to reduce recovery time.94 In studies comparing curcuminoids to NSAIDs, curcumin was equal in the improvement of pain with minimized long-term risk.83,95

Quercetin can help stabilize the release of histamine and be an alternative method to anti-inflammatory and antihistamine effects. Quercetin has also demonstrated therapeutic effects in treating inflammation from rheumatoid arthritis or wound healing, and has neuroprotective properties.96–98 Glucosamine also has potential for pain relief when treating osteoarthritis, inflammatory bowel disease, and migraines.99,100 Nutritional supplementation should always be guided by a qualified clinician who will be aware of potential interaction with other supplements or medications, including the possibility of hidden substances, in that supplements are regulated by the FDA not as drugs, but as food.


When given the opportunity to treat patients with SJH, proper precautions should be considered in parallel with treatment. Early detection of SJH is ideal, allowing the patient to consciously avoid collision sports. Activities that require high-impact movements can be dangerous for unstable joints. Repetitive use injuries should be avoided whenever possible, especially in overextended ranges of motion. Chronic overstretching can be harmful to nearby joints, ligaments, and nerves.

Knowledge of SJH and related conditions is paramount for surgeons and anesthesiologists caring for these complex patients. Surgical outcomes are suboptimal with increased occurrence of complications and poor wound healing.101,102 Surgical interventions may not address the underlying cause, which may require repeat surgeries. Those with EDS may be at increased risk of CRPS after limb injury or surgery.103 Procedural risks must be carefully considered. For example, animal studies have demonstrated the possibility of weakened connective tissue with repeated corticosteroid injections, without long-term procedural benefit.104,105 It is advised to avoid chiropractic adjustments (especially high-velocity ones) due to the sensitivity and instability related to joint hypermobility, especially patients with CCI and/or spinal instability.106 Finally, the lack of awareness and support for the SJH community has led to vulnerability through desperation. It is advised to be cautious of charlatans and products that make false claims. Treatment methods should be modified and adapted to suit the needs of the hypermobile individual. SJH is a complex medical condition that requires the guidance of a trained medical professional care team.


SJH is a frequently overlooked cause of pain in patients seeking care and pain management. When joint hypermobility is present in a patient, HSDs should be considered as a source of related symptoms. SJH cannot be detected in imaging or laboratory testing but through assessment of joints using the Beighton score, other tools for assessing generalized joint hypermobility, and examining tissue fragility and the skin. Pain management in patients with SJH requires a multimodal approach, such as the MENS PMMS method, to maintain lower pain levels, promote function, and facilitate abundant lives.


The authors acknowledge the Ehlers-Danlos Society for furthering research and awareness of EDS and related conditions, the Fullerton Foundation for support in educating the next generation of researchers and health care providers about EDS, and those with EDS and HSD who inspire them.


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