Neurosurgical Management of Cancer Pain

1. The purpose of this study was to investigate a proposed role for the postsynaptic dorsal column (PSDC) pathway in mediating visceral nociceptive input into the dorsal column (DC) nuclei. 2. In one group of animals, the hypogastric nerves were sectioned, thereby restricting colorectal input into the cord to pelvic afferent pathways known to coverage on lower lumbar and sacral segments. Extracellular recording were made from 41 nucleus gracilis (NG) cells that responded to colorectal distension (CRD). Results reported are from 15 NG cells that were tested before and after the administration of morphine into the sacral cord by microdialysis. 3. The responses of 11 NG cells to CRD were dramatically reduced by morphine infused into the sacral cord through a microdialysis fiber. This reduction was reversed by an intravenous injection of naloxone. Microdialysis administration of 6-cyano-7-nitro-quinoxaline-2,3-dione (CNQX) or a lesion of the DC also abolished the responses of the NG cells to CRD. 4. Four NG cells that responded to CRD showed an increase in their background activity approximately 25 min after an injection of mustard oil (MO). This increase in activity was counteracted by morphine or by a lesion of the DC. 5. In a second group of animals, recordings were made from 28 PSDC cells in the L0-S1 segments of the cord. These units were antidromically activated by stimulation of the upper cervical fasciculus gracilis. The projections of five PSDC neurons into the NG were traced with the use of antidromic mapping. Results are reported for the responses of 12 PSDC cells to CRD and to cutaneous stimuli before and after morphine administration into the sacral cord by microdialysis. 6. Morphine given spinally reduced the responses of 12 PSDC cells to CRD. This reduction was reversed by an intravenous injection of naloxone. CNQX administered spinally also abolished the responses to CRD of the PSDC cells tested. 7. Four other PSDC cells were studied before and after an injection of MO into the colon. Their background activity started to increase within 25 min after the injection. Morphine suppressed this increase in background activity and this effect of morphine was reversed by naloxone. 8. The responses of NG cells to cutaneous stimuli were not significantly affected by morphine in the dose used. On the other hand, morphine significantly reduced the responses of PSDC cells to noxious cutaneous stimuli although this effect was not as dramatic as that on responses to visceral stimuli. 9. From the results of the studies described in this and the companion paper, we conclude that there is an important pelvic visceral nociceptive pathway involving PSDC neurons that synapse in the NG. The NG in turn activates neurons in the ventral posterolateral (VPL) nucleus of the thalamus. We presume that activation of VPL neurons by noxious visceral stimulation contributes to visceral pain sensation and thus that pelvic visceral pain depends largely on activity in the DC-medial lemniscus system.

The present report provides evidence that axons in the medial part of the posterior column at T10 convey ascending nociceptive signals from pelvic visceral organs. This evidence was obtained from human surgical case studies and histological verification of the lesion in one of these cases, along with neuroanatomical and neurophysiological findings in animal experiments. A restricted lesion in this area can virtually eliminate pelvic pain due to cancer. The results remain excellent even in cases in which somatic structures of the pelvic body wall are involved. Following this procedure, neurological testing reveals no additional neurological deficit. There is no analgesia to pinprick stimuli applied to the body surface, despite the relief of the visceral pain. Since it is reasonable to attribute the favorable results of limited midline myelotomies to the interruption of axons of visceral nociceptive projection neurons in the posterior column, we have performed experiments in rats to test this hypothesis. The results in rats indicate that the dorsal column does indeed include a nociceptive component that signals pelvic visceral pain. The pathway includes neurons of the postsynaptic dorsal column pathway at the L6-S1 segmental level, axons of these neurons in the fasciculus gracilis, and neurons of the nucleus gracilis and the ventral posterolateral nucleus of the thalamus.