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A possible neurophysiological basis for psychological pain
Medical Hypotheses (1998) 51, 439--440
© HarcourtBrace& Co. Ltd 1998
Short Note: A possible neurophysiological basis for psychological pain T. KOYAMA Department of Anesthesiology, Osaka University Medical School, 2-2 Yamada-oka, Suita, Osaka, 565, Japan (Phone: +81 6 879 3133; Fax: +81 6 879 3139)
Abstract - - There is some evidence that the anterior cingulate cortex (ACC) contains nociceptive neurons, and other neurons which respond to conditioned aversive stimuli. It is not implausible that nociceptive input and conditioned aversive input converge onto common neurons in the ACC. Following from this hypothesis, the psychological pain which occurs in circumstances that arouse disgust or aversion may involve the same mechanisms that give rise to referred pain.
In clinics, physicians often see psychological pain patients who present no evidence of nociceptive events or organic lesions, and who tend to report pain sensations during events in their daily lives that arouse aversion or disgust. Since the experience of psychological pain is a complex integrated sensation that is dependent on higher brain functions such as learning, cognition and emotion, its neurophysiological basis is of much interest. Recent imaging studies with human subjects have shown the central representation of pain sensation. Nociceptive stimuli activate a number of cortical regions, including the primary somatosensory cortex, the secondary somatosensory cortex, the insular cortex and the anterior cingulate cortex (1,2). Among these cortical regions, the anterior cingulate cortex (ACC) is consistently activated, not only by nociceptive stimuli, but also by various kinds of pain syndrome (3), such as neuropathic pain (4) and cluster headache (5). As well as imaging studies, electrophysiological studies of anesthetized rats (6) and anesthetized rabbits (7) have found that some neurons in the ACC are nociceptive.
On the other hand, there are also studies which have shown that the ACC is deeply involved in aversive conditioning and discriminative avoidance learning. A human functional magnetic resonance imaging study (8) and electrophysiological studies on rabbit behavior (9,10) have found that the ACC is activated by conditioned aversive stimuli. Based on this evidence, it is possible to suggest that nociceptive sensory inputs and conditioned aversive sensory inputs converge onto common ACC neurons. According to this hypothesis, psychological pain may be explained by one of the same theories that accounts for referred pain. One of the physiological bases of referred pain is the projection--convergence theory (11-13) that takes into account the convergence of visceral and somatic primary sensory neurons onto common spinal neurons. The essence of the projection--convergence theory of referred pain is that the activity ascending from the spinal cord is misconstrued as originating from somatic structures (14). The ACC convergence hypothesis of aversive conditioned stimuli and nociceptive stimuli may offer a
Received24 April 1997 Accepted 12 June 1997 439
440
clue in the investigation of the neurophysiological basis of psychological pain: if there is convergence, environmental aversion stimuli may be misperceived as nociceptive, and this misconstruction may produce the sensation of pain in patients with psychological pain. A well-designed electrophysiological neuronal examination on whose behaviour is experimentally conditioned will test this hypothesis. References 1. Casey K L, Minoshima S, Morrow T J, Koeppe R A. Comparison of human cerebral activation patterns during cutaneous warmth, heat pain, and deep cold pain. J Neurophysiol 1996; 76: 571-581. 2. Coghill R C, Talbot J D, Evans A C, Meyer E, Gjedde A, Bushnell M C. Distributed processing of pain and vibration by the human brain. J Neurosci 1994; 14: 4095-4208. 3. Hsieh J C, Stahle-Backdahl M, Hagermark O, Stone-Elander S, Rosenquist G, Ingvar M. Traumatic nociceptive pain activates the hypothalamus and the periaqueductal gray: a positron emission tomography study. Pain 1995; 64: 303-314. 4. Hsieh J C, Belfrage M, Stone-Elander S, Hansson P, Ingvar M. Central representation of neuropathic pain studied by positron emission tomography. Pain 1995; 63: 225-236. 5. Hsieh J C, Halnnerz J, Ingvar M. Right-lateralised central processing for pain of nitroglycerin-induced cluster headache.
MEDICAL HYPOTHESES
Pain 1996; 67: 59~58. 6. Yamamura H, Iwata K, Tsuboi Y et al. Morphological and electrophysiologicai properties of ACCx nociceptive neurons in rats. Brain Res 1996; 735: 83-92. 7. Sikes R W, Vogt B A. Nociceptive neurons in area 24 of rabbit cingulate cortex. J Neurophysiol 1992; 68: 1720-1732. 8. Knight D C, Helmstetter F J, Stein E A. Functional imaging of brain regions involved in Pavlovian fear conditioning in humans. Soc Neurosci Abstr 1996; 22: 1867. 9. Freeman J H Jr, Cuppemell C, Flannery K, Gabriel M. Context-specific multi-site cingulate cortical, limbic thalamic, and hippocampal neuronal activity during concurrent discriminative approach and avoidance training in rabbits. J Neurosci 1996; 16: 1538-1549. 10. Kubota Y, Wolske M, Poremba A, Kang E, Gabriel M. Stimulus-related and movement-related single-unit activity in rabbit cingulate cortex and limbic thalamus during performance of discriminative avoidance behavior. Brain Res 1996; 721: 22-38. 11. Ruch T V. Howell's Textbook of Physiology. Philadelphia: W B Saunders,1947: 385-401. 12. Hancock M B, Foreman R D, Willis W D. Convergence of visceral and cutaneous input onto spinothalamic tract cells in the thoracic spinal cord of the cat. Exp Neurol 1975; 47: 240-248. 13. Cervero F, Tattersall J EH. Cutaneous receptive fields of somatic and viscerosomatic neurons in the thoracic spinal cord of the cat. J Comp Neurol 1985; 237: 325-332. 14. McMahon S B. Textbook of Pain, 3rd edn. Edinburgh: Churchill Livingstone, 1994: 129-151.
© HarcourtBrace& Co. Ltd 1998
Short Note: A possible neurophysiological basis for psychological pain T. KOYAMA Department of Anesthesiology, Osaka University Medical School, 2-2 Yamada-oka, Suita, Osaka, 565, Japan (Phone: +81 6 879 3133; Fax: +81 6 879 3139)
Abstract - - There is some evidence that the anterior cingulate cortex (ACC) contains nociceptive neurons, and other neurons which respond to conditioned aversive stimuli. It is not implausible that nociceptive input and conditioned aversive input converge onto common neurons in the ACC. Following from this hypothesis, the psychological pain which occurs in circumstances that arouse disgust or aversion may involve the same mechanisms that give rise to referred pain.
In clinics, physicians often see psychological pain patients who present no evidence of nociceptive events or organic lesions, and who tend to report pain sensations during events in their daily lives that arouse aversion or disgust. Since the experience of psychological pain is a complex integrated sensation that is dependent on higher brain functions such as learning, cognition and emotion, its neurophysiological basis is of much interest. Recent imaging studies with human subjects have shown the central representation of pain sensation. Nociceptive stimuli activate a number of cortical regions, including the primary somatosensory cortex, the secondary somatosensory cortex, the insular cortex and the anterior cingulate cortex (1,2). Among these cortical regions, the anterior cingulate cortex (ACC) is consistently activated, not only by nociceptive stimuli, but also by various kinds of pain syndrome (3), such as neuropathic pain (4) and cluster headache (5). As well as imaging studies, electrophysiological studies of anesthetized rats (6) and anesthetized rabbits (7) have found that some neurons in the ACC are nociceptive.
On the other hand, there are also studies which have shown that the ACC is deeply involved in aversive conditioning and discriminative avoidance learning. A human functional magnetic resonance imaging study (8) and electrophysiological studies on rabbit behavior (9,10) have found that the ACC is activated by conditioned aversive stimuli. Based on this evidence, it is possible to suggest that nociceptive sensory inputs and conditioned aversive sensory inputs converge onto common ACC neurons. According to this hypothesis, psychological pain may be explained by one of the same theories that accounts for referred pain. One of the physiological bases of referred pain is the projection--convergence theory (11-13) that takes into account the convergence of visceral and somatic primary sensory neurons onto common spinal neurons. The essence of the projection--convergence theory of referred pain is that the activity ascending from the spinal cord is misconstrued as originating from somatic structures (14). The ACC convergence hypothesis of aversive conditioned stimuli and nociceptive stimuli may offer a
Received24 April 1997 Accepted 12 June 1997 439
440
clue in the investigation of the neurophysiological basis of psychological pain: if there is convergence, environmental aversion stimuli may be misperceived as nociceptive, and this misconstruction may produce the sensation of pain in patients with psychological pain. A well-designed electrophysiological neuronal examination on whose behaviour is experimentally conditioned will test this hypothesis. References 1. Casey K L, Minoshima S, Morrow T J, Koeppe R A. Comparison of human cerebral activation patterns during cutaneous warmth, heat pain, and deep cold pain. J Neurophysiol 1996; 76: 571-581. 2. Coghill R C, Talbot J D, Evans A C, Meyer E, Gjedde A, Bushnell M C. Distributed processing of pain and vibration by the human brain. J Neurosci 1994; 14: 4095-4208. 3. Hsieh J C, Stahle-Backdahl M, Hagermark O, Stone-Elander S, Rosenquist G, Ingvar M. Traumatic nociceptive pain activates the hypothalamus and the periaqueductal gray: a positron emission tomography study. Pain 1995; 64: 303-314. 4. Hsieh J C, Belfrage M, Stone-Elander S, Hansson P, Ingvar M. Central representation of neuropathic pain studied by positron emission tomography. Pain 1995; 63: 225-236. 5. Hsieh J C, Halnnerz J, Ingvar M. Right-lateralised central processing for pain of nitroglycerin-induced cluster headache.
MEDICAL HYPOTHESES
Pain 1996; 67: 59~58. 6. Yamamura H, Iwata K, Tsuboi Y et al. Morphological and electrophysiologicai properties of ACCx nociceptive neurons in rats. Brain Res 1996; 735: 83-92. 7. Sikes R W, Vogt B A. Nociceptive neurons in area 24 of rabbit cingulate cortex. J Neurophysiol 1992; 68: 1720-1732. 8. Knight D C, Helmstetter F J, Stein E A. Functional imaging of brain regions involved in Pavlovian fear conditioning in humans. Soc Neurosci Abstr 1996; 22: 1867. 9. Freeman J H Jr, Cuppemell C, Flannery K, Gabriel M. Context-specific multi-site cingulate cortical, limbic thalamic, and hippocampal neuronal activity during concurrent discriminative approach and avoidance training in rabbits. J Neurosci 1996; 16: 1538-1549. 10. Kubota Y, Wolske M, Poremba A, Kang E, Gabriel M. Stimulus-related and movement-related single-unit activity in rabbit cingulate cortex and limbic thalamus during performance of discriminative avoidance behavior. Brain Res 1996; 721: 22-38. 11. Ruch T V. Howell's Textbook of Physiology. Philadelphia: W B Saunders,1947: 385-401. 12. Hancock M B, Foreman R D, Willis W D. Convergence of visceral and cutaneous input onto spinothalamic tract cells in the thoracic spinal cord of the cat. Exp Neurol 1975; 47: 240-248. 13. Cervero F, Tattersall J EH. Cutaneous receptive fields of somatic and viscerosomatic neurons in the thoracic spinal cord of the cat. J Comp Neurol 1985; 237: 325-332. 14. McMahon S B. Textbook of Pain, 3rd edn. Edinburgh: Churchill Livingstone, 1994: 129-151.