International Association for the Study of Pain 9th World Congress on Pain.Vienna, Austria. August 22–27, 1999.
What happens when approximately 6,000 researchers and clinicians from all over the world come together once every 3 yr to discuss the latest developments in pain research and treatment? Excitement, enthusiasm, optimism, realism, and plenty of discussion, sometimes heated. This large meeting in a picturesque city, with > 1,500 abstracts presented, several dozen topical workshops, and many plenary lectures, had something for everyone interested in pain research and treatment. Following are a few highlights of the meeting from the perspective of these reviewers. Some of these advances are presented in more detail in a recent supplement to Pain (Supplement 6, August 1999), an issue dedicated to the contributions of Dr. Patrick Wall to the pain field.
Peripheral Afferent Neurophysiology
The theme of this meeting, dedicated to Patrick Wall, was clearly plasticity in physiology and pharmacology that underlies chronic pain. Among the new topics reviewed in plasticity of the peripheral afferent was molecular characterization of Na+channels, especially by C fibers, which are responsible for initiation and maintenance of conduction of nerve activity related to nociception. Steven Waxman (Yale University) described the variety of Na+-channel subtypes expressed in the peripheral nervous system and how these subtypes change after nerve injury. These studies underlie the concept of development of drugs to selectively target channels expressed only in “pain” fibers or those that are expressed only in the setting of nerve injury and pain. A variety of other pharmacologic studies targeting the peripheral afferent to relieve pain were presented or reviewed, including description of κ opioid receptors on visceral afferents and the role of inflammatory mediators and receptors in sustained pain. Promising preliminary data were presented on a parenteral, second-generation cyclooxygenase-2 antagonist that was effective in reducing postoperative pain but did not affect platelet function or the gastrointestinal mucosa.
Spinal Cord Neurophysiology
Alan Basbaum (University of California, San Francisco) provided an outstanding review of how genetic manipulations in mice (knockouts, knockdowns, or knockins) have allowed a dissection of the receptors responsible within the spinal cord that initiate or maintain chronic pain states after nerve injury or inflammation. Clinical trials demonstrated efficacy of a variety of N -methyl-D-aspartate antagonists in the treatment of chronic pain, but usually accompanied by side effects. Other clinical trials described efficacy of spinally administered neostigmine, clonidine, and adenosine in hyperalgesic states, as well as sustained release preparations of opioids for oral or epidural administration. The role of prostaglandin synthesis in sensitization of the spinal cord was discussed, and the possible spinal mechanism of action in cyclooxygenase inhibitors in relieving pain was highlighted.
Descending Modulation of Pain
The simple concept that the brain or brainstem sends inhibitory signals to dampen the response to pain is being replaced by reverberating circuits of inhibitory and facilitatory signals from the brainstem to the spinal cord. Thus, development or maintenance of chronic pain states can be facilitated or inhibited by various descending systems, and the underlying circuitry explaining these responses is becoming clearer. The ongoing debate on whether pain is mediated by dedicated neural pathways, and the reasons for the considerable gap between our understanding of the sensation of pain compared with other sensations such as vision or hearing, were the topic of an intellectual and passionate discussion that involved distinguished investigators such as Drs. Devor, Wall, Ochoa, and Perl.
Gender and Developmental Effects
Maria Fitzgerald (University College, London) chaired a workshop on the developmental aspects of pain that were also featured in several abstracts. The timing of development of peripheral afferents and their neurochemistry were discussed, as well as responsiveness to painful stimulation and analgesics. A developing theme relevant to anesthesia and pediatric practice is the long-lasting enhanced responses to noxious stimuli that can occur after early neonatal exposure to repeated painful procedures or conditions. Karen Berkley (Florida State University, Tallahassee) chaired workshops and a special-interest group on the role of sex and gender in pain responses. Abstract presentations and these sessions highlighted major sex differences in pain syndromes, response to analgesics, and mechanisms of hyperalgesia that are being explored.
Genetics of Pain
Differences in response of individual patients to analgesics have often been explained by ethnic or pharmacokinetic differences. Dr. Mogil (University of Illinois at Urbana–Champaign) provided data from extensive studies in various mice species that suggest that pain sensitivity, response to analgesics, and susceptibility to painful pathologies may be a result of genetic differences. An understanding of the genetic factors that lead to interindividual differences in analgesic needs of patients could potentially allow idiosyncratic, patient-centered pain management.
Animal Models versus Clinical Pain States?
The validity and relevance of animal models of acute and chronic clinical pain states were discussed in plenary lectures and workshops. Dr. Koltzenburg (University of Würzburg) highlighted the discrepancies between animal models of neuropathic pain and the clinical situation. For example, only a small subset of nerve injuries in humans leads to persistent pain, whereas almost all animals with partial nerve injuries develop neuropathic pain behavior. In addition, the limitations of animal models in predicting the clinical efficacy and side-effect profile of new classes of drugs were discussed. For example, although substance P has been long recognized as an important excitatory neurotransmitter in the spinal cord involved in pain, acting on neurokinin receptors, the pilot clinical studies with neurokinin antagonists have not been successful. Raymond Hill (Merck, Sharp, and Dohme Research Laboratories, Essex, United Kingdom) chaired a workshop discussing the possible reasons for this failure to develop a “magic bullet.” The message was that although preclinical pharmacologic studies in animal models are extremely helpful as screening tools, the clinical efficacy and safety of the drugs need to be confirmed with carefully performed clinical trials.
Mechanisms-based Pain Classification Scheme
In a topical workshop chaired by Dr. Dubner (University of Maryland Dental School), a plea was made to the clinicians to adapt a pain classification scheme that was based on mechanisms rather than on causes, e.g. , neuropathic pain with A-fiber–mediated touch-evoked allodynia versus traumatic neuropathic pain. In an attempt to develop such a classification, Dr. Woolf (Massachusetts General Hospital) suggested that clinicians should carefully characterize the patient’s spontaneous and stimulus-evoked pains to different mechanical and thermal stimuli. Dr. Bennett (Allegheny University) pointed out that pharmacologic studies in animal models of neuropathic pain have shown that different drugs attenuate different aspects of the pain behavior to varying degrees. The concept of combination therapies with agents that would target specific aspects of the overall pain, i.e. , ongoing pain or allodynia to dynamic mechanical stimuli, was introduced.
There was a sense of disheartenment among clinicians that despite dramatic advances in our understanding of the basic mechanisms of pain and its alteration after tissue injury, the advances in the clinical management of chronic pain was less striking. However, experts in the pain field were optimistic that basic science and clinical evidence-based research are likely to result in the development of novel therapeutic strategies in the near future.