- Email: [email protected]
Hyperalgesia and allodynia: Pathogenesis and mechanisms
Reviews
244
and consider marital counseling. The outcome with 100 Jobs could have been rewritten in modem times as 50 curse God and die, 40 modify their behavior, nine go to another clinic, and one faces the whirlwind of God. I recommend this book to the pain specialist in order to understand some of the ways in which pain relates directly to literature, sexuality, surgery, esthetics, etc. This is an ambitious book. It is characteristic of the author’s style to interweave topics and examples from several different eras. This style makes the book very enlightening and entertaining, but also somewhat exasperating. As a reader, I found that I had to catch up with Mr. Morris’s ideas. In conclusion, this book is full of clinical pearls well worth the effort of collecting.
Hyperalgesia and Allodynia Robert j. Schwartzman,
MD
H$eralgesia and Allodyn.ia:Pathogenesis and Mechanisms
(The Bristol-Myers Squibb Symposium on Pain Research) Edited by William D. Willis Published by Raven Press, New York 1992,400 pages, $98.00 Hyjmalgesia and Allodynia is the product of the Bristol-Myers Squibb Symposium of Pain Research. In this volume, a vast array of basic science and clinical information has been analyzed and brought to bear on the mechanisms underlying hyperalgesia, an increased sensitivity to painful stimuli, and allodynia, which is pain evoked by ordinarily innocuous stimuli. It is clear that these two phenomena have both peripheral and central components. Recent investigations have demonstrated that a variety of chemical substances at the site of tissue injury (histamine, H+, bradykinin, prostaglandins) sensitize primary nociceptors through secondary messenger systems. Evidence is reviewed that demonstrates a subpopulation of nociceptors that are unresponsive to
Robert J. Schwartzman, MD, is Professor and Chairman, Department of Neurology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.
Vol.8 No. 4 May 1993
noxious stimuli under physiologic conditions (sleeping nociceptors) but respond after sensitization by inflammation. Chemical mediators of hyperalgesia in areas I:~ inflammation may act through neuropeptidcs by the release of cytokines (leukotriene B4) from neutrophils that in turn release other compounds, such as 8R, 15-S, di HETE, that sensitize nociceptors. Nociceptor sensitization has been demonstrated in patients with allodynia and hyperalgesia and plays a role in varied clinical conditions where these twc. symptoms are prominent. The anatomic, pharmacologic, and physiologic studies that underlie the interaction of neuropeptides and excitatory amino acids at the dorsal horn (DH) are analyzed in detail. A large percentage of dorsal root ganglion cells contain glutamate immunoreactivity and 25% of these cells colocalize substance P. They may also coexist in C-fiber primary afferents. Small dorsal root ganglion cells and their synapses also contain immunoreactivity for aspartate. There may be independent release of these neuropeptides following nerve or tissue damage that could independently activate AMPA, NMDA, and NK-1 receptors, which would initiate the cascade of physiologic events ending in sensitization of central pain-projecting neurons. A mechanism for central sensitization evaluated in the text is that SP release from C-fiber primary afferents depolarizes a group of DH interneurons whose projections remove the voltage gated Mg2+ block of the NMDA receptor in the CPP neuron. This results in an increase of cytosolic calcium which activates intracellular phospholipases and protein kinases that further transform the excitability of the CPP neuron. NMDA receptors have tIeen linked to the important “wind-up” phenomena of CPP neurons both by metabotropic glutamate receptors and by peptide-initiated signal-transducing mechanisms. An exciting new concept of act!vity&pendent neural plasticity is discussed in relation to the activation of early response genfs by painful stimuli and their consequent effect on dorsal horn physiology. Painful stimuli or transection of the sciatic nerve induces the expression of Cfos in spinal dorsal horn reurons. The C-fos gene regulates other genes and has a half-life of only 4 hr. Thus, if it is expressed days or weeks after injury, it marks the cells involved in a painful chronic condition. Recent evidence reviewed
VOL8 No. 4 May I993
suggests that C-j& expression may be modified by NMDA receptor blockade. C-j0 regulation of both dynorphin and enkephalin may influence the spontaneous activity of CPP neurons and en!arge their receptive fields. Several chapters in the text explore and analyze the clinical and experimental data
Reviews
245
that support sensitization of DH projection neurons as a major component of allodynia and hyperalgesia. This volume is extremely well written and edited and will be invaluable for all clinicians who treat pain as well as those experimentalists who study it.
244
and consider marital counseling. The outcome with 100 Jobs could have been rewritten in modem times as 50 curse God and die, 40 modify their behavior, nine go to another clinic, and one faces the whirlwind of God. I recommend this book to the pain specialist in order to understand some of the ways in which pain relates directly to literature, sexuality, surgery, esthetics, etc. This is an ambitious book. It is characteristic of the author’s style to interweave topics and examples from several different eras. This style makes the book very enlightening and entertaining, but also somewhat exasperating. As a reader, I found that I had to catch up with Mr. Morris’s ideas. In conclusion, this book is full of clinical pearls well worth the effort of collecting.
Hyperalgesia and Allodynia Robert j. Schwartzman,
MD
H$eralgesia and Allodyn.ia:Pathogenesis and Mechanisms
(The Bristol-Myers Squibb Symposium on Pain Research) Edited by William D. Willis Published by Raven Press, New York 1992,400 pages, $98.00 Hyjmalgesia and Allodynia is the product of the Bristol-Myers Squibb Symposium of Pain Research. In this volume, a vast array of basic science and clinical information has been analyzed and brought to bear on the mechanisms underlying hyperalgesia, an increased sensitivity to painful stimuli, and allodynia, which is pain evoked by ordinarily innocuous stimuli. It is clear that these two phenomena have both peripheral and central components. Recent investigations have demonstrated that a variety of chemical substances at the site of tissue injury (histamine, H+, bradykinin, prostaglandins) sensitize primary nociceptors through secondary messenger systems. Evidence is reviewed that demonstrates a subpopulation of nociceptors that are unresponsive to
Robert J. Schwartzman, MD, is Professor and Chairman, Department of Neurology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.
Vol.8 No. 4 May 1993
noxious stimuli under physiologic conditions (sleeping nociceptors) but respond after sensitization by inflammation. Chemical mediators of hyperalgesia in areas I:~ inflammation may act through neuropeptidcs by the release of cytokines (leukotriene B4) from neutrophils that in turn release other compounds, such as 8R, 15-S, di HETE, that sensitize nociceptors. Nociceptor sensitization has been demonstrated in patients with allodynia and hyperalgesia and plays a role in varied clinical conditions where these twc. symptoms are prominent. The anatomic, pharmacologic, and physiologic studies that underlie the interaction of neuropeptides and excitatory amino acids at the dorsal horn (DH) are analyzed in detail. A large percentage of dorsal root ganglion cells contain glutamate immunoreactivity and 25% of these cells colocalize substance P. They may also coexist in C-fiber primary afferents. Small dorsal root ganglion cells and their synapses also contain immunoreactivity for aspartate. There may be independent release of these neuropeptides following nerve or tissue damage that could independently activate AMPA, NMDA, and NK-1 receptors, which would initiate the cascade of physiologic events ending in sensitization of central pain-projecting neurons. A mechanism for central sensitization evaluated in the text is that SP release from C-fiber primary afferents depolarizes a group of DH interneurons whose projections remove the voltage gated Mg2+ block of the NMDA receptor in the CPP neuron. This results in an increase of cytosolic calcium which activates intracellular phospholipases and protein kinases that further transform the excitability of the CPP neuron. NMDA receptors have tIeen linked to the important “wind-up” phenomena of CPP neurons both by metabotropic glutamate receptors and by peptide-initiated signal-transducing mechanisms. An exciting new concept of act!vity&pendent neural plasticity is discussed in relation to the activation of early response genfs by painful stimuli and their consequent effect on dorsal horn physiology. Painful stimuli or transection of the sciatic nerve induces the expression of Cfos in spinal dorsal horn reurons. The C-fos gene regulates other genes and has a half-life of only 4 hr. Thus, if it is expressed days or weeks after injury, it marks the cells involved in a painful chronic condition. Recent evidence reviewed
VOL8 No. 4 May I993
suggests that C-j& expression may be modified by NMDA receptor blockade. C-j0 regulation of both dynorphin and enkephalin may influence the spontaneous activity of CPP neurons and en!arge their receptive fields. Several chapters in the text explore and analyze the clinical and experimental data
Reviews
245
that support sensitization of DH projection neurons as a major component of allodynia and hyperalgesia. This volume is extremely well written and edited and will be invaluable for all clinicians who treat pain as well as those experimentalists who study it.