262 Based on our animal data and limited human trials, we believe continuous infusions of intrathecal octreotide are safe. Randomized, double-blind trials using larger numbers of patients are necessary to further establish the efficacy and safety of intrathecal octreotide. Unfortunately, current availability of octreotide is limited and use of the commercially available formulation would exceed $20.000 annually.
References Leblanc, R., Gauthier. S., Gamin, M., Quirion, R.. Palmour, R. and Masson, H., Neurobehavioral effects on intrathecal somatostatinergic treatment in subhuman primates, Neurology, 38 (1988) 1887-1890. Penn. R.D., Paice, J.A. and Kroin, J.S., Octreotide: a potent new non-opiate analgesic for intrathecal infusion. Pain. 49 (1992) 13-19.
Richard D. Penn Judith A. Paice Jeffrey S. Kroin
This model, and many other current models of pain perception based on the ‘sensitization of the WDRs’, leave the brain stem, the thalamus, the limbic system, the cortex and all the other bits and pieces of the brain with very little to do. There is no room left for the higher centres (or lower centres in Price et al.‘s diagrams) in the processing of pain signals. That some people, including virtually all politicians, do not need a brain to go about their business is sadly evident. but isn’s it too much to expect that all pain is in the spinal cord’? We need to include supraspinal structures in our models of pain processing and we should stop peddling these ultra-specificity no tions by which if a spike occurs in a spinal cord cell (preferably a WDR) the perception of pain inevitably ensues. Max von Frey himself would have been very proud of these models. There must be a half way between Descartes’ well known representation of the spinal cord as just a transmission nerve and this exclusive role in pain perception given nowadays to spinal mechanisms. Incidentally. whatever happened to nociceptor-specific cells’? They do not even feature in Price et al.‘s model. But this, as they say, is another story.
References
PAIN 02180
Price, D.D.. Long, S. and Huitt. C., Sensory testing of pathophyxiological mechanisms of pain in patients with reflex sympathetic dystrophy, Pain, 49 (1992) 163-173.
Fernando
Cervero
Not all pain is in the spinal cord I am used to getting a certain amount of stick from the gurus of pain research for my having dared to suggest that the processing of nociceptive signals retains some specificity in its central organisation. So. imagine my surprise when I read the recent paper by Price et al. (1992) proposing an ultra-specificity model for the central processing of pain. Since none of the aforementioned gurus even raised an eyebrow at such temerity, here is this letter to redress the balance. The paper in question is a psychophysical study of pain sensation in patients suffering from reflex sympathetic dystrophy (RSD). I have no qualms about the study itself, barring a minor quibble about the use of the term ‘high threshold allodynia’. As allodynia is meant to imply that innocuous stimuli evoke pain; ‘high-threshold allodynia’ is at best ambiguous. But this is not the reason for my writing this letter so let’s get on with the real business. The problem is the model, or series of models, that Price et al. propose as possible mechanisms for the pain sensations observed in their patients. These models are all centred around a class of spinal cord neurone known as wide-dynamic-range cell (WDR) which, in the opinion of the authors, becomes a pain-cell extraordinaire. According to the model, if the peripheral input to WDR cells is dominated by nociceptor activity, as they suggest happens under normal circumstances, then you will feel normal pain. However, if the WDRs are activated by low-threshold mechanoreceptors, as they propose may happen in some cases of RSD, then you get lowthreshold allodynia. Furthermore, if the almighty WDRs are driven by enhanced activity in nociceptors then you will get high-threshold allodynia. The only role left to the rest of the CNS in this model is to follow blindly what these pain cells in the spinal cord dictate. The pain signal is processed and packaged by the WDRs and is then projected along a labelled line to the brain where all that is needed, I assume. is some kind of spike-perception convertor. Enigmatically, the WDR cells in Price et al.‘s diagrams project downwards (!) towards the brain.
PAIN 02181
Reply to F. Cervero Dr. Cervero has probably misunderstood and misrepresented the purpose of our explanatory models in our recent paper (Price et al., 1992, Fig. 2, page 171). The purpose of these models was simply to provide a general explanation of bofh peripheral and some central pathophysiological mechanisms that are likely to underlie some of the symptoms of reflex sympathetic dystrophy (RSD) and neuropathic pain encountered in our studies. The models focus on primary afferents and the spinal cord because the vast majority of current knowledge of pathophysiological mechanisms of neuropathic pain includes these two levels. One only has to peruse all of the issues of PAIN and other leading neuroscience journal issues published since 1988 (when the Bennett and Xie model was published) to see much of the evidence for this. That the spinal cord dorsal horn in general and wide-dynamicrange (WDR) sensory transmission neurons in particular have crucial roles in these pathophysiological mechanisms is supported by considerable evidence. To take just one of several examples from the literature, a recent paper by Palecek et al. (1992) shows that WDR neurons increase their spontaneous activity and become hyper-responsive to innocuous brushing after an experimental neuropathy is produced in the rat, a result consistent with A-beta allodynia in some patients. This is precisely the kind of result that would be expected. based on our model (no. II) in Fig. 2. Interestingly, nociceptivespecific and low-threshold neurons did not become nearly as pathologically altered as did the WDR neurons. Consistent with this
References Leblanc, R., Gauthier. S., Gamin, M., Quirion, R.. Palmour, R. and Masson, H., Neurobehavioral effects on intrathecal somatostatinergic treatment in subhuman primates, Neurology, 38 (1988) 1887-1890. Penn. R.D., Paice, J.A. and Kroin, J.S., Octreotide: a potent new non-opiate analgesic for intrathecal infusion. Pain. 49 (1992) 13-19.
Richard D. Penn Judith A. Paice Jeffrey S. Kroin
This model, and many other current models of pain perception based on the ‘sensitization of the WDRs’, leave the brain stem, the thalamus, the limbic system, the cortex and all the other bits and pieces of the brain with very little to do. There is no room left for the higher centres (or lower centres in Price et al.‘s diagrams) in the processing of pain signals. That some people, including virtually all politicians, do not need a brain to go about their business is sadly evident. but isn’s it too much to expect that all pain is in the spinal cord’? We need to include supraspinal structures in our models of pain processing and we should stop peddling these ultra-specificity no tions by which if a spike occurs in a spinal cord cell (preferably a WDR) the perception of pain inevitably ensues. Max von Frey himself would have been very proud of these models. There must be a half way between Descartes’ well known representation of the spinal cord as just a transmission nerve and this exclusive role in pain perception given nowadays to spinal mechanisms. Incidentally. whatever happened to nociceptor-specific cells’? They do not even feature in Price et al.‘s model. But this, as they say, is another story.
References
PAIN 02180
Price, D.D.. Long, S. and Huitt. C., Sensory testing of pathophyxiological mechanisms of pain in patients with reflex sympathetic dystrophy, Pain, 49 (1992) 163-173.
Fernando
Cervero
Not all pain is in the spinal cord I am used to getting a certain amount of stick from the gurus of pain research for my having dared to suggest that the processing of nociceptive signals retains some specificity in its central organisation. So. imagine my surprise when I read the recent paper by Price et al. (1992) proposing an ultra-specificity model for the central processing of pain. Since none of the aforementioned gurus even raised an eyebrow at such temerity, here is this letter to redress the balance. The paper in question is a psychophysical study of pain sensation in patients suffering from reflex sympathetic dystrophy (RSD). I have no qualms about the study itself, barring a minor quibble about the use of the term ‘high threshold allodynia’. As allodynia is meant to imply that innocuous stimuli evoke pain; ‘high-threshold allodynia’ is at best ambiguous. But this is not the reason for my writing this letter so let’s get on with the real business. The problem is the model, or series of models, that Price et al. propose as possible mechanisms for the pain sensations observed in their patients. These models are all centred around a class of spinal cord neurone known as wide-dynamic-range cell (WDR) which, in the opinion of the authors, becomes a pain-cell extraordinaire. According to the model, if the peripheral input to WDR cells is dominated by nociceptor activity, as they suggest happens under normal circumstances, then you will feel normal pain. However, if the WDRs are activated by low-threshold mechanoreceptors, as they propose may happen in some cases of RSD, then you get lowthreshold allodynia. Furthermore, if the almighty WDRs are driven by enhanced activity in nociceptors then you will get high-threshold allodynia. The only role left to the rest of the CNS in this model is to follow blindly what these pain cells in the spinal cord dictate. The pain signal is processed and packaged by the WDRs and is then projected along a labelled line to the brain where all that is needed, I assume. is some kind of spike-perception convertor. Enigmatically, the WDR cells in Price et al.‘s diagrams project downwards (!) towards the brain.
PAIN 02181
Reply to F. Cervero Dr. Cervero has probably misunderstood and misrepresented the purpose of our explanatory models in our recent paper (Price et al., 1992, Fig. 2, page 171). The purpose of these models was simply to provide a general explanation of bofh peripheral and some central pathophysiological mechanisms that are likely to underlie some of the symptoms of reflex sympathetic dystrophy (RSD) and neuropathic pain encountered in our studies. The models focus on primary afferents and the spinal cord because the vast majority of current knowledge of pathophysiological mechanisms of neuropathic pain includes these two levels. One only has to peruse all of the issues of PAIN and other leading neuroscience journal issues published since 1988 (when the Bennett and Xie model was published) to see much of the evidence for this. That the spinal cord dorsal horn in general and wide-dynamicrange (WDR) sensory transmission neurons in particular have crucial roles in these pathophysiological mechanisms is supported by considerable evidence. To take just one of several examples from the literature, a recent paper by Palecek et al. (1992) shows that WDR neurons increase their spontaneous activity and become hyper-responsive to innocuous brushing after an experimental neuropathy is produced in the rat, a result consistent with A-beta allodynia in some patients. This is precisely the kind of result that would be expected. based on our model (no. II) in Fig. 2. Interestingly, nociceptivespecific and low-threshold neurons did not become nearly as pathologically altered as did the WDR neurons. Consistent with this
