Different Types of Pain in Complex Regional Pain Syndrome Require a Personalized Treatment Strategy

Figures & data

Table 1 Definition and Grading System of Nociceptive, Neuropathic, and Nociplastic Pain

	Nociceptive Pain	Neuropathic Pain	Nociplastic Pain
Definition	Pain that arises from actual or threatened damage to non-neural tissue and is due to the activation of nociceptors^Citation15	Pain caused by a lesion or disease of the somatosensory nervous system^Citation15,Citation41	Pain that arises from altered nociception despite no clear evidence of actual or threatened tissue damage causing the activation of peripheral nociceptors or evidence for disease or lesion of the somatosensory system causing the pain^Citation15,Citation56
	Pain associated with active inflammation falls into the category of nociceptive pain^Citation19
Grading system: Possible		History of relevant neurological lesion or disease Pain distribution neuroanatomically plausible^Citation42	Pain >3 months Regional rather than discrete No nociceptive or neuropathic pain Evoked pain hypersensitivity phenomena^Citation59
Grading system: Probable		Sensory signs in neuroanatomically plausible distribution during physical examination^Citation42	History of pain hypersensitivity and comorbidities^Citation59
Grading system: Definite		Confirmed lesion or disease of the somatosensory nervous system by a diagnostic test^Citation42

Figure 1 Pain types in Complex Regional Pain Syndrome.

Notes: Pain types experienced by CRPS patients can be differentiated in the pain types that are recognized for chronic pain by the International Association for the Study of Pain: nociceptive, neuropathic and nociplastic pain. The most prominent pain type should be targeted to optimize the treatment effectiveness. Nociceptive, neuropathic and nociplastic pain are linked to underlying pathophysiological mechanisms that contribute to Complex Regional Pain Syndrome.

Table 2 Underlying Mechanisms, Diagnostic Instruments, and Treatments That Can Be Linked to Nociceptive, Neuropathic, and Nociplastic Pain in CRPS

Types of Pain Recognized by IASP	Evidence in CRPS	Diagnostic Instruments	Treatment
Nociceptive pain	Inflammation^Citation23,Citation26	Physical examination: tumor, dolor, calor, rubor and functio laesa	Physical therapy and rehabilitation^Citation7,Citation104 Psychological treatment^Citation7,Citation105 World Health Organization analgesic ladder medication^Citation38 Immunomodulating drugs^Citation39,Citation40
		Inflammation biomarkers^Citation35
	Contractures^Citation32	Physical examination: fixed flexion postures	Physical therapy and rehabilitation^Citation7,Citation104 Psychological treatment^Citation7,Citation105
	Dystonia^Citation32	Physical examination: fixed flexion postures. Passive stretching of the affected digits should incite a contraction of the stretched muscle implying stretch reflex hyperexcitability^Citation32	Physical therapy and rehabilitation^Citation7,Citation104 Anti-spasmolytics^Citation32 Psychological treatment^Citation7,Citation105
Neuropathic pain	Major nerve lesions	Physical examination: pain in neuroanatomical distribution PainDETECT^Citation43 and DN4 questionnaire^Citation44 Electromyography, magnetic resonance imaging	Physical therapy and rehabilitation^Citation7,Citation104 Psychological treatment^Citation7,Citation105 Antidepressants or anticonvulsants^Citation55 Neurostimulation^Citation106–108
	Small fiber neuropathy^Citation50	Quantitative sensory testing, skin biopsy
Nociplastic pain	Central sensitization^Citation65,Citation66	Physical examination: more widespread allodynia/hyperalgesia Michigan Body Map^Citation61 Quantitative sensory testing, temporal summation^Citation65,Citation71 Conditioned pain modulation^Citation72	Physical therapy and rehabilitation^Citation7,Citation104 Psychological treatment^Citation7,Citation105 Antidepressants or anticonvulsants^Citation55 Intravenous ketamine^Citation88 Neurostimulation^Citation106–108

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