Complex regional pain syndrome (CRPS)
Complex regional pain syndrome (CRPS) is a chronic disorder of dysregulated pain processing that typically follows an injury — a wrist fracture, a sprain, a surgical procedure, sometimes a frank nerve injury — and produces pain wildly out of proportion to the inciting event, plus sensory disturbances (hyperalgesia, allodynia), vasomotor changes (skin color, temperature asymmetry), sudomotor changes (sweating, edema), and over time motor and trophic changes (atrophy, contracture, abnormal nail and hair growth). It's classified as Type I when there's no major nerve injury (the older 'reflex sympathetic dystrophy' / RSD label) and Type II when a major nerve injury is identifiable (the older 'causalgia' label). Diagnosis is clinical, based on the Budapest Criteria; there's no specific biomarker. Treatment is anchored by early mobilization and structured PT — immobilization makes outcomes worse — supplemented by pain neuroscience education, mirror therapy and graded motor imagery, neuropathic analgesics, sympathetic blocks, ketamine infusions in selected cases, and neuromodulation (dorsal root ganglion stimulation, spinal cord stimulation) for refractory disease. The peptide community is unusually active on CRPS, which is the reason this page exists — not to recommend peptides, but to be honest about why they don't address what CRPS actually is. RSDSA + IASP + American Academy of Pain Medicine. Thirty-eighth deliberate non-elevation.
What changes during this transition
CRPS gets a substrate page in the Juno library — as the 38th deliberate non-elevation of the life-stage program — for a specific reason: it is one of the conditions where peptide marketing meets desperate patients with particular intensity, and the editorial honest answer is that the peptides being marketed don't reach the pathophysiology that defines the disease. The pathophysiology matters. CRPS is fundamentally a disorder of central and peripheral sensitization. After an initial injury — and the inciting injury can be remarkably minor; wrist fractures, ankle sprains, and minor surgical procedures account for most cases — the nociceptive system fails to return to baseline. Dorsal horn neurons in the spinal cord become hyperexcitable. Somatosensory cortex undergoes maladaptive reorganization, often with the cortical representation of the affected limb shrinking or distorting. Autonomic dysregulation produces the vasomotor and sudomotor features. Trophic changes accumulate over months: muscle atrophy from disuse driven by pain avoidance, skin thinning, abnormal nail and hair growth, sometimes contracture. The pain is the dominant feature throughout — spontaneous, often burning or aching, often with hyperalgesia (amplified response to noxious stimuli) and allodynia (pain from non-noxious stimuli like light touch or clothing brushing the skin). The treatment that moves outcomes is not pharmacological in the sense most patients arrive expecting. The single most load-bearing intervention is early mobilization and structured physical or occupational therapy — the affected limb has to be used, loaded, moved through range. The 'use it or lose it' threshold is real and time-sensitive. Every week of reduced loading deepens the cortical reorganization, deepens the disuse atrophy, deepens the motor neglect. Mirror therapy and graded motor imagery — protocols developed by Moseley and others over the past two decades — specifically target the cortical reorganization, with the strongest evidence among non-pharmacological interventions. Pain neuroscience education, where patients learn what's actually happening in their nervous system and reframe pain as a danger signal that's miscalibrated, supports the rest of the program psychologically. Pharmacologically, neuropathic analgesics (gabapentin, pregabalin, tricyclic antidepressants, SNRIs) are first-line. Topical capsaicin and lidocaine help in some patients. IV regional blocks (Bier blocks), sympathetic blocks (stellate ganglion for upper extremity, lumbar sympathetic for lower) are diagnostic and therapeutic — particularly useful in the early 'warm' phase. Ketamine infusions at sub-anesthetic and (in specialty centers) anesthetic doses have emerging evidence in refractory cases. Bisphosphonates (alendronate, pamidronate) have evidence in early CRPS with bone scan changes. Vitamin C 500 mg/day for 50 days after distal radius fracture — the Zollinger trial — is one of the few preventive interventions with evidence. For refractory cases, neuromodulation with dorsal root ganglion stimulation (Abbott Proclaim DRG is FDA-approved specifically for CRPS of the lower limbs) or spinal cord stimulation can be transformative. In specialty centers, immunotherapy with IVIG has small-trial signal and rituximab is investigational for a subset of patients with suspected autoimmune contribution. What doesn't move CRPS outcomes is the peptide market. BPC-157 is sold into CRPS communities under a 'nerve healing' framing that misrepresents what CRPS is — the substrate isn't a structural nerve injury that hasn't healed; it's a nervous system in a dysregulated sensitized state. TB-500 is sold under a 'tissue regeneration' framing for the atrophy and trophic changes — but those features are downstream of disuse and autonomic dysregulation, not a structural tissue-repair deficit. Cerebrolysin's neurotrophic program is real and multi-jurisdictionally established in stroke and TBI, but the CRPS register doesn't exist and the mechanism leap from recovery plasticity to maladaptive plasticity isn't trivial. LL-37 routes into 'autoimmune-flavored' framings that intersect uncomfortably with the unresolved autoimmune-CRPS hypothesis. NMN extends general-aging NAD+ marketing toward 'nerve rejuvenation' the molecule has no clinical-endpoint data to support. We include CRPS in the library because users are asking — and because the right answer for them is a clear one: the interventions with CRPS-specific evidence are the ones that should occupy the treatment plan, and peptides being marketed for CRPS are not among them.
Important caveat
This entry is not medical advice and is particularly load-bearing for CRPS because the condition attracts unusually active peptide marketing and the gap between marketing claim and pathophysiology is unusually wide. The editorial position is direct: peptides currently marketed for CRPS — BPC-157, TB-500, Cerebrolysin off-register, LL-37, NMN — do not address the central and peripheral sensitization, the cortical reorganization, the autonomic dysregulation, or the motor neglect that define the disease. The interventions that do belong in a CRPS treatment plan are anchored by EARLY MOBILIZATION + STRUCTURED PHYSICAL THERAPY (load-bearing — immobilization worsens outcomes), mirror therapy and graded motor imagery, pain neuroscience education and cognitive-behavioral therapy for pain, neuropathic analgesics (gabapentin, pregabalin, tricyclic antidepressants, SNRIs), topical agents (capsaicin, lidocaine), and where indicated sympathetic blocks (stellate ganglion for upper extremity, lumbar sympathetic for lower extremity), Bier blocks, ketamine infusions, bisphosphonates in early CRPS with bone scan changes, and neuromodulation (dorsal root ganglion stimulation per the Abbott Proclaim DRG FDA approval, spinal cord stimulation, peripheral nerve stimulation) for refractory disease. The single most important intervention is the one that's hardest to do — using the affected limb, loading it through pain, attending PT consistently. Every week of immobilization makes the outcome worse, and the peptide community framings that route patients toward injectable substrates and away from PT attendance are doing measurable harm. PARTICULAR VIGILANCE ON BPC-157 MARKETING — the peptide is one of the most aggressively marketed in CRPS spaces under a 'nerve healing' framing that misrepresents what CRPS is. If you have CRPS or suspect you do, the right care team is a pain medicine specialist, a PT or OT with CRPS-specific experience, a pain psychologist for the pain neuroscience education component, and depending on presentation an interventional pain specialist for blocks and ketamine, a neurosurgeon or interventional pain specialist for neuromodulation evaluation in refractory cases, and where the autoimmune-CRPS hypothesis seems clinically suggestive, a rheumatologist or neuroimmunologist familiar with the IVIG and rituximab literature. None of that team should be a 'peptide clinic.' Pediatric CRPS has better prognosis than adult CRPS but the same treatment anchor — intensive PT — applies, often through specialized pediatric pain programs. Vitamin C 500 mg/day for 50 days post-distal-radius-fracture is one of the few prevention-stage interventions with evidence (Zollinger trial). WADA athletes: BPC-157 (S0) and TB-500 (S2) prohibited at all times. The Reflex Sympathetic Dystrophy Syndrome Association (RSDSA), the International Association for the Study of Pain (IASP), and the American Academy of Pain Medicine maintain patient resources that map the evidence-based pathway honestly.
Want this list to grow? The library is editorial — if there’s a peptide you think belongs on this page with documented or mechanistically-clear evidence, send us a note with the citation and we’ll review it under the same evidence-tier discipline as every other entry.