478 



HANDBOOK OF PHYSIOLOGY 



NEUROPHYSIOLOGY I 



Hyperalgesic State After Trauma 



We may now consider the special studies of Lewis 

 (171) on the hyperalgesic state provoked in skin by 

 controlled scratching, heat, freezing, ultraviolet 

 light, or chemical or electrical irritation. These 

 varied forms of trauma all produce a skin which is 

 hyperalgesic in the strict sense of the word, i.e. a 

 lighter needle prick will cause pain from it than from 

 corresponding normal skin. In addition, an effective 

 prick gives unusually intense, diffuse and long-lasting 

 pain. Spontaneous pain is present which is worsened 

 by relatively small amounts of warmth, more marked 

 cooling or light contacts such as those from clothing. 

 The zone of hyperalgesia gradually spreads after the 

 injury — for example five minutes of faradization of 

 the skin a little above the wrist provoked the above 

 change over an area 18 cm long with a maximal 

 width of 7 cm, an extent achieved within 1 1 min. 

 (171, p. 69). The soreness in the area lasted several 

 hours. Some days later repetition of the stimulation 

 procedure led to nearly the same pattern of hyper- 

 algesic zone. In general, such zones tend to corre- 

 spond to the entire area of a cutaneous nerve, as 

 shown by their agreement with the area of sensory 

 elimination after anesthetic block of the nerve trunk. 

 Moreover, direct stimulation of the cutaneous nerve 

 trunk or any of its smaller branches will evoke the 

 typical hyperalgesic pattern. Lewis advanced the 

 view that a pain-producing substance developed at 

 the site of injury which, by stimulus to local nerves, 

 provoked the reaction over the whole arborization 

 of a single cutaneous nerve. He also hypothecated 

 that such reactions must be mediated by a new and 

 distinct system of fibers which he called 'nocifensor' 

 nerves. He was especially led to this conclusion by the 

 fact that the pain terminals arising from a single 

 nerve fiber have never been demonstrated histo- 

 logically to cover so large an area as, e.g. 7x18 

 cm on the forearm. Maruhashi et al. (185) have come 

 close to this electrophysiologically however. They 

 found individual afTerent fibers in the cat innervating 

 oval areas ranging from 3x5 to 5x9 cm. Such 

 fibers to which they give the special designation 'wide 

 receptive fibers' were abundant in all skin nerves 

 examined; they ranged from 2 to 5 /j in diameter. 

 These fibers are probaljly not identifiable with the 

 nocifensor system since afferent impulses can be 

 evoked in them by 'extremely light touch' to the 

 skin or to a hair in the fiber's large receptive field. 

 Moreover such responses persist in areas 'deaffer- 

 ented' by excision of five lumbar root ganglia 3 to 



4 wk. before the experiment. On the contrary the 

 post-traumatic hyperalgesia of Lewis disappears 

 from zones denervated by posterior rhizotomy. In 

 the absence of any anatomical demonstration of an 

 entirely different system of fibers specialized to medi- 

 ate the hyperalgesic spread, this concept of nocifensor 

 fibers has won little support. Walshe (282) and 

 White & Sweet (296, p. 96) may be consulted for 

 further arguments /)/o but mainly con. 



CHEMIC.'\L EXCIT.XNTS OF P.MN 



The concept that chemicals liberated at the site 

 of injury provoke pain has been supported experi- 

 mentally by Lewis (171, pp. 113 to 115). His extracts 

 of freshly excised human skin caused pain when in- 

 jected in tiny quantities intradermally. He thought 

 the substance was not histamine since he found 

 this to give itching rather than pain when it was 

 pricked into the skin even in such high concentra- 

 tion as 1:30. Rosenthal (226), however, found that 

 "as little as fifty-four molecules of histamine" in- 

 jected intradermally will cause pain, and in a series 

 of papers with several collaborators has presented 

 evidence that histamine or a similar substance is the 

 chemical mediator for cutaneous pain. Moreover 

 Habgood's (113) analyses of the substance liberated 

 upon antidromic stimulation of frog cutaneous nerve 

 pointed toward histamine or an 'H-substance.' In 

 addition he demonstrated that the chemical so 

 produced could often evoke spontaneous discharge 

 from an adjacent nerve twig (fig. 6). That a similar 

 phenomenon may take place in man is intimated by 

 Foerster's observations upon stimulation of distal 

 ends of divided posterior roots at operation. This 

 provoked burning pain in the skin which was elimi- 

 nated by division of adjoining posterior roots. If 

 then antidromically-induced liberation of a chem- 

 ical which stimulates nerve endings will activate a 

 separate but overlapping sensory unit, a wide area 

 would be involved by a continuation of this process. 

 The extent of the spread would tend to increase with 

 the extent and .severity of the original injur\-. .^nd 

 since Lewis had already obtained hyperalgesia by 

 antidromic stimulation of cutaneous nerves in man, 

 its explanation would not require either a separate 

 system of nocifensor nerves or the wide receptive 

 fibers of Maruhashi et al. (185). 



The technique of applying fluids to the exposed 

 base of a blister caused by cantharidin or heat, de- 

 veloped by Keele and his a.ssociates, has enabled 



