Analgesia from rostral brain stem stimulation in the rat

Rats implanted with bipolar stimulating electrodes in the rostral medial brain stem were tested for brain stimulation-produced analgesia using tail-flick, pinch and hot-plate tests. Potent analgesia across all three tests was obtained from stimulation of sites in the gray matter surrounding the aqueduct and the caudal portion of the third ventricle, the posterior hypothalamus, the midline area of the caudal thalamus and the pretectal region of the meso-diencephalic junction. The analgesia obtained from these sites was comparable to that produced by stimulation of the previously studied caudal periaqueductal gray matter: it outlasted the period of brain stimulation, was not due to a generalized motor debilitation of the animal, and was not correlated with changes in electrographic activity. Stimulation of sites in the caudal thalamus and pretectal area yielded analgesia without stimulation-induced aversive reactions, confirming the potential of these sites for use in the relief of clinical pain in man.

[1]  H. Akil,et al.  Pain reduction by electrical brain stimulation in man. Part 1: Acute administration in periaqueductal and periventricular sites. , 1977, Journal of neurosurgery.

[2]  J. O’Keefe,et al.  Reversal of morphine and stimulus-produced analgesia by subtotal spinal cord lesions , 1977, Pain.

[3]  J. O'Callaghan,et al.  Quantification of the analgesic activity of narcotic antagonists by a modified hot-plate procedure. , 1975, The Journal of pharmacology and experimental therapeutics.

[4]  E. S. Gurdjian.  The diencephalon of the albino rat . Studies on the brain of the rat. No. 2 , 1927 .

[5]  D. Mayer,et al.  Pain reduction by focal electrical stimulation of the brain: an anatomical and behavioral analysis , 1974, Pain.

[6]  Donald D. Price,et al.  Central nervous system mechanisms of analgesia , 1976, Pain.

[7]  B. Hamilton,et al.  Efferent connections of the periaqueductal gray matter in the cat , 1970, The Journal of comparative neurology.

[8]  T. Yaksh,et al.  Localization of the antinociceptive action of morphine in primate brain , 1975, Pharmacology Biochemistry and Behavior.

[9]  G. W. Beeler,et al.  Reciprocal (push-pull) effects of morphine on single units in the ventromedian and lateral hypothalamus and influences on other nuclei: with a comment on methadone effects during withdrawal from morphine. , 1974, Brain research.

[10]  S. Snyder,et al.  Regional Distribution of Opiate Receptor Binding in Monkey and Human Brain , 1973, Nature.

[11]  D. V. Reynolds,et al.  Surgery in the Rat during Electrical Analgesia Induced by Focal Brain Stimulation , 1969, Science.

[12]  A. Lajtha,et al.  Paradoxical Effects after Microinjection of Morphine in the Periaqueductal Gray Matter in the Rat , 1974, Science.

[13]  B Carder,et al.  Analgesia from Electrical Stimulation in the Brainstem of the Rat , 1971, Science.

[14]  S. Irwin,et al.  The effects of morphine methadone and meperidine on some reflex responses of spinal animals to nociceptive stimulation. , 1951, The Journal of pharmacology and experimental therapeutics.

[15]  C. Leonard,et al.  Connections of the median and dorsal raphe nuclei in the rat: An autoradiographic and degeneration study , 1974, The Journal of comparative neurology.

[16]  W. Krieg.  The medial region of the thalamus of the albino rat , 1944 .

[17]  Fred E. D'Amour,et al.  A METHOD FOR DETERMINING LOSS OF PAIN SENSATION , 1941 .

[18]  Johnn E. Adams,et al.  Naloxone reversal of analgesia produced by brain stimulation in the human , 1976, Pain.

[19]  D. Bodian.  Studies on the diencephalon of the Virginia opossum. Part II. The fiber connections in normal and experimental material , 1940 .

[20]  H. Akil,et al.  Pain reduction by electrical brain stimulation in man. Part 2: Chronic self-administration in the periventricular gray matter. , 1977, Journal of neurosurgery.

[21]  J. Hughes.  Isolation of an endogenous compound from the brain with pharmacological properties similar to morphine , 1975, Brain Research.

[22]  J. Liebeskind,et al.  Effects of pain-attenuating brain stimulation and morphine on electrical activity in the raphe nuclei of the awake rat , 1977, Pain.

[23]  A. Lajtha,et al.  Morphine Action at Central Nervous System Sites in Rat: Analgesia or Hyperalgesia Depending on Site and Dose , 1973, Science.

[24]  J. Sutin.  The periventricular stratum of the hypothalamus. , 1966, International review of neurobiology.

[25]  S. Balagura,et al.  The analgesic effect of electrical stimulation of the diencephalon and mesencephalon. , 1973 .

[26]  E. Anderson,et al.  Morphine analgesia: Blockade by raphe magnus lesions , 1975, Brain Research.

[27]  R. Guillery.  Degeneration in the hypothalamic connexions of the albino rat. , 1957, Journal of anatomy.

[28]  L. Pellegrino,et al.  stereotaxic atlas of the rat brain , 1967 .

[29]  B. Hamilton.  Projections of the nuclei of the periaqueductal gray matter in the cat , 1973, The Journal of comparative neurology.

[30]  J. Oliveras,et al.  Analgesia induced by electrical stimulation of the inferior centralis nucleus of the raphe in the cat , 1975, PAIN.

[31]  D. Rioch.  Studies on the diencephalon of Carnivora. Part III. Certain myelinated‐fiber connections of the diencephalon of the dog (Canis familiaris), cat (Felis domestica), and aevisa (Crossarchus obscurus) , 1931 .

[32]  E. Crosby,et al.  The mammalian midbrain and isthmus regions. Part II. The fiber connections. C. The hypothalamo‐tegmental pathways , 1951, The Journal of comparative neurology.

[33]  H. Akil,et al.  Monoaminergic mechanisms of stimulation-produced analgesia , 1975, Brain Research.

[34]  T. Yaksh,et al.  Sites of morphine induced analgesia in the primate brain: relation to pain pathways. , 1974 .

[35]  W. Y. Soper.  Effects of analgesic midbrain stimulation on reflex withdrawal and thermal escape in the rat. , 1976, Journal of comparative and physiological psychology.

[36]  O. Lindvall,et al.  The adrenergic innervation of the rat thalamus as revealed by the glyoxylic acid fluorescence method , 1974, The Journal of comparative neurology.

[37]  A. Wikler,et al.  Effects of Morphine on Cortical Electrical Activity of the Rat * , 1944, The Yale journal of biology and medicine.

[38]  C. C. Chi.  An experimental silver study of the ascending projections of the central gray substance and adjacent tegmentum in the rat with observations in the cat , 1970 .

[39]  T. Yaksh,et al.  Systematic examination in the rat of brain sites sensitive to the direct application of morphine: Observation of differential effects within the periaqueductal gray , 1976, Brain Research.

[40]  T. Cicero,et al.  Analgesia and hyperreactivity produced by intracranial microinjections of morphine into the periaqueductal gray matter of the rat. , 1974, Behavioral biology.

[41]  K. Tsou,et al.  STUDIES ON THE SITE OF ANALGESIC ACTION OF MORPHINE BY INTRACEREBRAL MICRO-INJECTION. , 1964, Scientia Sinica.