1995). These cases did not contribute to the weight of mechanistic evidence. In addition, Kachko et al. (2007) attributed the development of CRPS to Crohn’s disease. These publications did not contribute to the weight of mechanistic evidence.

Described below are publications reporting clinical, diagnostic, or experimental evidence that contributed to the weight of mechanistic evidence.

Jastaniah et al. (2003) described four patients who developed complex regional pain syndrome after vaccination against hepatitis B. Case 2 described a 12-year-old girl presenting with swelling, decreased temperature, discoloration, and loss of function of the left arm lasting for 1 week. Symptom onset developed 30 minutes after receiving the first dose of a hepatitis B vaccine in the left deltoid muscle. The same symptoms developed within minutes and lasted for 1 week after administration of the second dose of a hepatitis B vaccine in the right arm. The patient was afflicted by two additional episodes developing spontaneously; one involved the development of an urticarial rash and pain in the left foot, the second involved swelling, pallor, coolness, and pain in the left arm and hand. Case 4 describes a 12-year-old girl presenting with discoloration, swelling, and the inability to clench the fingers of the right hand 15 minutes after receiving the first dose of a hepatitis B vaccine in the right deltoid muscle. Past history revealed an episode of leg swelling after injection of the first dose of a diphtheria-tetanus-pertussis vaccine in the thigh; no other physical exam findings were consistent with CRPS. Subsequent pertussis vaccines were withheld and the patient tolerated other vaccinations without incident.

Ali et al. (2000) conducted a study to determine if peripheral administration of physiologically relevant doses of an α-adrenergic agonist resulted in pain in patients with sympathetically maintained pain. Twelve individuals with either type I or type II CRPS affecting either an upper or a lower extremity and normal individuals were recruited to take part in the study. The participants diagnosed with CRPS previously underwent local anesthetic blocks of the sympathetic ganglia. Each participant received saline, and three concentrations of norepinephrine were administered via intradermal injection twice each. One series of injections was administered on the unaffected extremity in the mirror image region to the area on the affected extremity. Pain to each of the injections was rated by the participant. Subsequently, the same series of injections were administered on the affected extremity, and the participants rated pain to each of the injections. None of the concentrations of norepinephrine elicited pain in the normal participants. Likewise, none of the concentrations of norepinephrine elicited significant pain in the participants diagnosed with CRPS when injected into the unaffected side. In contrast, the two highest concentrations of norepinephrine elicited significant pain in comparison to saline when injected in the affected extremity.

Mailis-Gagnon and Bennett (2004) conducted a study using normal



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