Pii: S0304-3959(01)00439-0

Venipuncture, the most frequently performed invasive medical procedure (Horowitz, 1994), is usually benign, producing only transitory mild discomfort. However, several case series (Berry and Wallis, 1977; Newman and Waxman, 1996; Horowitz, 1994, 2000; Newman, 2001) and individual patient reports (see Horowitz, 1994) document nerve injuries consequent to the procedure. While such injuries are reportedly rare, 1:21 000–26 700 (Berry and Wallis, 1977; Newman and Waxman, 1996) or 1:6250–6928 (Newman, 2001), some can be severe with permanent residua, the most disturbing being chronic neuropathic pain – the Complex Regional Pain Syndrome Type 2 (CRPS-II), or causalgia. It is defined (Merskey and Bogduk, 1994), as a persistent shooting, electrical, burning pain in the distribution of the affected nerve with frequent spread to adjoining areas, often in association with autonomic and motor dysfunctions. Recent articles in this journal (Eliav et al., 1999; Pitcher et al., 1999; Li et al., 2000; Eschenfelder et al., 2000; Decosterd and Woolf, 2000; Han et al., 2000; Liu et al., 2000a,b,c; Habler et al., 2000; Lindenlaub and Sommer, 2000), employing various peripheral nerve injury models and methodologies in the rat, have studied the pathophysiology of injury-induced neuropathic pain and associated phenomena (mechanosensitivity, allodynia, hyperalgesia). While sites and types of experimental injury differ, each study links the pain to ectopic discharges in primary afferent neurons and ‘central sensitization’, i.e. increased excitability of spinal cord dorsal horn neurons – changes in receptive field properties, decreased thresholds and increased responsiveness to peripheral input (Woolf, 1996). Two sources of discharges are currently favored (Gold, 2000): (1) injured afferent fibers at the lesion site and/or their dorsal root ganglia (DRG) soma (Devor and Seltzer, 1999; Han et al., 2000; Liu et al., 2000a,c); or (2) uninjured afferent fibers consequent to peripheral interactions with injured afferents undergoing Wallerian degeneration (Li et al., 2000; Eschenfelder et al., 2000). In either case, post-injury, spontaneous pain appears due to spontaneous electrogenesis, and pain with movement or palpation secondary to mechanosensitivity at these sites. Innocuous or noxious stimulation in the dermatomal distribution of surviving uninjured Ab low threshold afferent mechanoreceptors trigger heightened sensitivity (allodynia or hyperalgesia, respectively) (Woolf, 1996), due to spinal amplification. This central sensitization may be initiated and maintained by peripheral impulse generation (‘ectopia’) from injured fibers (Devor and Seltzer, 1999; Tal et al, 1999; Liu et al., 2000b), or, conversely, a loss of input to the dorsal horn (deafferentation hypersensitivity) (Eschenfelder et al., 2000). Venipuncture-induced CRPS-II/causalgia is, perhaps, the most paradigmatic human neuropathic pain that can follow acute nerve trauma. It has many similarities to the experimental situation: the procedure – venipuncture – and instrument involved – hypodermic needle – are always identical; the exact timing of injury is known; and the same cutaneous sensory nerves are always involved, i.e. medial or lateral antebrachial cutaneous nerves in the antecubital fossa, superficial radial nerve at the wrist, or dorsal sensory nerves of the hand. As our current concepts of the pathophysiology and treatment of human neuropathic pain are inadequate, it is useful to relate the hypotheses discussed to the clinical venipuncture syndrome, specifically the onset and duration of symptoms and signs, type of nerve fibers affected, and sympathetic nervous system effects.