Continuing pain, which is disproportionate to any inciting event
At least one symptom in three (clinical diagnostic criteria) or four (research diagnostic criteria) of the following categories:
(a) Sensory: hyperesthesia or allodynia
(b) Vasomotor: temperature asymmetry, skin color changes, or skin color asymmetry
(c) Sudomotor or edema: edema, sweating changes, or sweating asymmetry
(d) Motor or trophic: decreased range of motion, motor dysfunction (weakness, tremor, or dystonia), or trophic changes (hair, nails, or skin)
At least one sign at the time of diagnosis in two or more of the following categories:
(a) Sensory: hyperalgesia (to pinprick) or allodynia (to light touch, deep somatic pressure, or joint movement)
(b) Vasomotor: temperature asymmetry, skin color changes or asymmetry
(c) Sudomotor or edema: edema, sweating changes, or sweating asymmetry
(d) Motor or trophic: decreased range of motion, or motor dysfunction (weakness, tremor, or dystonia), or trophic changes (hair, nails, or skin)
No other diagnosis better explains the signs and symptoms
Three stages of the CRPS are recognized. Stage 1 (acute phase) is characterized by pain, swelling, warming, and redness of the extremity. In stage 2 (dystrophic phase), the extremity becomes cool and cyanotic and shows trophic changes of hairs and nails, osteoporosis, stiffness, and muscle weakness. Stage 3 (atrophic phase) occurs when atrophy of bones, muscles, and skin become irreversible.
Three-phase bone scintigraphy can support the diagnosis providing evidence of typical bone changes. CRPS requires a differential diagnosis with neuropathic pain syndromes, vascular diseases, inflammatory and myofascial disorders, and psychiatric diseases.
40.5.4 Treatments and Prognosis
Bisphosphonates and physical therapy to inhibit bone reabsorption, antiepileptic, antidepressant and opioids to control pain, and interventional therapies including nerve blockade, sympathetic (stellate ganglion) block, and sympathectomy have been reported to provide beneficial effects in patients. However, the management of CRPS requires a multidisciplinary approach including also psychological (pain coping skills, relaxation, and biofeedback) and rehabilitation treatments.
The incidence of severe complications of stellate ganglion block (e.g., bupivacaine, botulin toxin), mostly caused by inadvertent injection of the subarachnoid space, arteria vertebralis, or thoracic pleural cavity, has been estimated in 1.7/1,000 patients. Horner’s syndrome and hoarseness caused by spreading of the anesthetic drug along the sympathetic cervical trunks or laryngeus recurrens nerve can occur.
Follow-up studies demonstrated that CRPS can have a highly variable course. Some patients experience a brief syndrome resolving in 6–12 months with minimal sequelae (weakness and stiffness), whereas others complain of long-lasting symptoms with chronic pain. Peripheral autonomic symptoms (vasomotor and sudomotor changes) most commonly recover in early stages, whereas skin trophic changes and motor symptoms (weakness, stiffness, dystonia) can persist also over years. Table 40.2 reports the prognostic factors of CRPS.
Factors influencing the prognosis of CRPS
Prognostic factors in CRPS
Predictors of poor outcome
Predictors of good outcome
Longer pain duration
Fracture as trigger event
Absence of sensory symptoms
Presence of swelling
Warm limb in early stages
Poorer grip strength and mobility
Early onset after tissue injury
The recovery rate of CRPS was reported to range from 74 % in the first year to 36 % within 6 years. Severe CRPS outcome was reported to be rare, although most patients can experience persistent impairments at 2 or more years since onset. In a case series of 102 patients assessed at 5.8 years (range: 2.1–10.8) since onset, 16 % complained of progressive CRPS and 31 % could not work. Poorest outcome is associated with upper extremity involvement, trigger other than a fracture, and cold CRPS .
40.6 Phantom Pain
Phantom pain is a complex of sensation related to the removal of a part of the body. This phenomenon typically occurs after a limb amputation, but may also develop after radical surgery of other parts of the body, such as tongue, eyes, penis, or breast, after nerve or brachial plexus avulsion or spinal cord injury . It has been described in about 20 % of children with congenital limb aplasia.
40.6.2 Clinical Features
About 70 % of patients can experience phantom pain (e.g., shooting, stabbing, squeezing, or burning) immediately after the amputation, whereas 84 % of patients experience phantom sensations, namely, sensory illusions of the removed limb in the form of cold or warm feelings, itch, or tingling. These are part of the large spectrum of symptoms, which includes kinetic (movement) and kinesthetic (positional orientation) sensations. Patients can experience phantom movement (often referred to as painful spasm) and some are able to move the phantom at will. The phantom limb can assume unnatural positions in the space, such as outstretch in front, behind, or sideways. Telescoping is another perception reported as the phantom limb seems shortened and it feels like only the digits remain on the stump.
Treatment of phantom pain is based on a multidisciplinary approach including neuropathic pain drugs (antidepressants, anticonvulsant, and opioids), physical therapies (acupuncture, ultrasound, TENS, motor, cortex, and spinal cord stimulation), rehabilitation programs, and, in a very limited number of critical patients, surgical treatments (revision of the stump, dorsal column tractotomy, dorsal root entry zone lesions) .
Phantom limb pain can spontaneously improve or resolve, but it persists over 2 years in 60 % of patients and is referred as severe in 0.5–5 %.
40.7 Painful Neuroma
The abnormal growth of Schwann cells and nerve fibers that can occur after a peripheral nerve injury is known as traumatic neuroma. It represents the ineffective attempt of regeneration and can develop in any nerve. Typical examples are Morton’s neuroma (usually affecting the common digital nerve in the third planter space) or amputation neuroma (involving the distal stump of the truncated nerve). Pain has the features of neuropathic pain and the efficacy of the pharmacological treatments is often poor .
40.7.2 Treatments and Prognosis
Neuroma formation should be prevented in the case of predetermined surgical nerve injury (e.g., amputation) or surgical revision. Surgical approaches include relocating the nerve stump into an environment (such as bone, muscle, or vein) far from the original injury site and protecting the nerve from further injuries. In these cases, success rate with partial pain relief is 50–60 % .
40.8 Central Post-Stroke Pain
Central post-stroke pain (CPSP) is a condition arising as a consequence of a cerebrovascular disease. In the past, this condition was known as “Dejerine–Roussy syndrome” and strictly related to a thalamic stroke. The definition of CPSP has been currently extended and includes the whole somatosensory pathway as a possible site of injury.
40.8.2 Clinical Features
CPSP shows a neuroanatomic distribution that corresponds to the damaged central nervous system (CNS) area. It should not be confused with other common post-stroke pain syndromes, such as shoulder pain, headache, or painful spasticity. The estimated prevalence of CPSP varies between 11 and 55 %, a wide range likely due to the lack of well-defined diagnostic criteria. Most commonly, CPSP occurs a few months after the CNS injury, although it can develop either immediately after the cerebrovascular event or years later.
40.8.3 Treatments and Prognosis
CPSP is difficult to treat and has a poor outcome.
Pharmacological treatments have limited efficacy despite multi-drug therapy (e.g., antidepressants, anticonvulsant, and opioids).
Neurostimulation targeting the sensory thalamus has shown a success rate of 45–50 % at 1-year follow-up . The factors predisposing to the development of central pain after stroke are still unknown. A recent study found that patients with a lesion in the posterior and lateral thalamus have an increased risk to develop CPSP than those with anterior-medial lesions .
40.9 Postherpetic Neuralgia (PHN)
Terminology and definitions – Pain in the territory of a cranial nerve or dermatome previously affected by Herpes Zoster infection, lasting >3 months after rash onset.
Clinical features – Spontaneous (burning, stabbing, paroxysmal, itching) and evoked (light touch and pressure allodynia) neuropathic pain; possible motor involvement with waste and weakness. Facial weakness, corneal damage, vertigo and ipsilateral hearing loss, tinnitus may be present, according to Zoster localization.
Diagnosis – Based on clinical and anamnestic information. No laboratory test is necessary.
Top Differential Diagnoses – Herpes simplex virus, impetigo, candidiasis, contact dermatitis, insect bites, autoimmune blistering disease, dermatitis herpetiformis, drug eruptions.
Principles of treatment – Tricyclic antidepressants, gabapentinoids, and topical lidocaine are first-line treatments.
Prognosis – Pain can recover within 3 months from rash onset in most patients <50 years. PHN develop in 5 % of patients <60 years, 10 % of patients between 60 and 70, and in 20 % of patients aged 70 years or older. About 3 % of patients can experience PHN after 1 year. Live attenuated vaccine can reduce significantly the risk incidence of both HZ and PHN.
Postherpetic neuralgia (PHN) is the most common complication of Herpes Zoster (HZ) infection and is defined as pain in the territory of a cranial nerve or dermatome lasting more than 3 months after skin rash onset.
The overall incidence of HZ infection ranges between 1.2 and 3.4 per 1,000 persons per years. Its frequency increased with aging from 2 cases per 1,000 persons under 50 years to 10 cases per 1,000 between 70 and 80 years. About 50 % of individuals who reach age 85 years may have had at least one episode of Herpes Zoster. Elderly and immunocompromised patients are at higher risk. PHN shows a similar age-related increase of incidence, from 5 % in subjects younger than 60 years to 10 % in those aged 60–69 years and up to 20 % in those aged 80 years or older .