Ascending Pathways for Itch

A large number of studies published over the last 75 years indicate that, in addition to blocking pain, ventral lateral cordotomies (surgical disruption of the ventral lateral funiculus) also consistently block the sensation of itch. Such studies are taken as evidence supporting an important role for the spinothalamic tract (STT) in pruriception since its axons ascend within the VLF. Banzet (1927) first reported that cordotomy abolished pruritus. He noted that severe itch caused by irritation of the vulva was completely relieved following a ventral lateral cordotomy and recommended cordotomy as a treatment for the problem. Hyndman and Wolkin (1943) carefully studied the responses of ten cordotomy patients to the pruritic compound cowhage. They found that cowhage did not produce itch in the areas rendered analgesic in any of the patients but did produce itch in areas in which pain sensation was normal. These authors concluded that “it can be said with certainty that the sensation of itch is mediated through the spinothalamic tract” (Hyndman and Wolkin 1943, p. 130). White et al. (1950) reported that a patient who had undergone a cordotomy did not experience itch in the analgesic area of the body even following contact with poison ivy. These authors also noted that in another patient severe itching caused by a intramedullary neoplasm of the spinal cord was abolished by a cordotomy and that their patients were not “annoyed by the itch” following the bite of a mosquito. Foerster (1936), Graf (1960), and Taren and Kahn (1966) also reported that cordotomies blocked the sensation of itch. Therefore, these clinical studies showed that, in addition to information related to pain and temperature sensation, axons in the ventral lateral funiculus (VLF) convey information that is necessary for production of the sensation of itch. It should be noted that electrophysiological studies of neurons in other spinal pathways that send ascending axons within the VLF, such as the spinoparabrachial, spinomesencephalic, spinoreticular, and spinohypothalamic tracts, have not yet been carried out. Axons in any, or all, of these pathways may also carry pruriceptive information to any number of areas of the brain and thereby contribute to sensory-discriminative, autonomic, affective, or modulatory systems related to itch. The responses of STT neurons to pruritic stimuli have been examined in several electrophysiological studies. Wei and Tuckett (1991) examined the responses of individual axons ascending within the VLF of cats to the nonhistaminergic pruritic agent cowhage. The spinal cords of the cats were cut at C1 to ensure that all axons that responded to the stimuli were ascending within the VLF. It was not possible in this study to determine whether the examined units were axons of the STT of any of the other pathways within the VLF. The responses of 34 axons classified as wide dynamic range (WDR) (i.e., responding to innocuous and noxious stimuli) were compared following application of inactive (boiled) and active cowhage to their receptive fields. Almost all units were activated by the insertion of either inactive or active cowhage. A majority of the examined units exhibited significantly increased levels of firing for minutes following removal of the active, but not the inactive, cowhage spicules. These findings showed that mechanically sensitive neurons are capable of carrying pruriceptive information and therefore support the idea that neurons that respond to nociceptive stimuli might also be capable of carrying pruriceptive information. It appears that no attempt was made in this study to determine whether any axons in the VLF were insensitive to mechanical stimuli. This study also provided additional evidence that pruriceptive information ascends within the VLF; this is indirect support for the idea that the STT is involved in pruriception. Andrew and Craig (2001) examined responses of mechanically insensitive spinothalamic tract neurons in the lumbar spinal cord of cats. A small number of such cells were found. Four responded to iontophoretic application of histamine. Two of these were also activated by application of mustard oil, a noxious stimulus. The authors concluded sensory information about itch was carried by STT axons that responded only to pruriceptive stimuli. Responses to injections of capsaicin were not examined nor were the responses of mechanically sensitive nociceptive neurons to application of histamine.