Specific thalamic nuclei function as novel ‘nociceptive discriminators’ in the endogenous control of nociception in rats

Recently, we hypothesized that supraspinal structures may have important functions in discriminating between noxious mechanically and heat mediated nociception through distinct functions: facilitation and inhibition. In this study, conducted in conscious rats, we explored the role of different thalamic nuclei: the mediodorsal (MD) nucleus, the central medial (CM) nucleus, the submedius (SM) nucleus, the ventralmedial (VM) nucleus and the ventral posterolateral (VPL) nucleus, in the descending control of secondary and contralateral mechanical hyperalgesia and heat hypoalgesia occurring in intramuscularly hypertonic (HT, 5.8%) saline-induced muscle nociception. We found that the MD nuclei participated in the descending facilitation of mechanical hyperalgesia, and that the VM nuclei were specifically involved in the descending inhibition of heat hypoalgesia. Neither descending facilitation nor descending inhibition was affected after electrolytic lesion of the thalamic CM, SM, and VPL nuclei. This descending facilitatory and inhibitory modulation of nociception was strengthened by glutamate, and weakened by GABA, microinjected into the thalamic MD and VM nuclei. It is suggested that (1) thalamic MD nucleus and VM nucleus form two distinct endogenous systems in the control of noxious mechanically and heat evoked responses, and (2) the strengthening of descending inhibition and the weakening of descending facilitation by means of up regulation and down regulation of appropriate receptor expression in the VM and MD nuclei may provide a new strategic policy in treating pathological pain.

[1]  G. Holmes,et al.  Sensory disturbances from cerebral lesions , 1911 .

[2]  M. Zimmermann,et al.  Ethical guidelines for investigations of experimental pain in conscious animals , 1983, Pain.

[3]  Allan I. Basbaum,et al.  Central nervous system mechanisms of pain modulation , 2006 .

[4]  A. Basbaum,et al.  Reflex neurogenic inflammation. I. Contribution of the peripheral nervous system to spatially remote inflammatory responses that follow injury , 1985, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[5]  J. Dostrovsky,et al.  Responses of neurons in the rat thalamic nucleus submedius to cutaneous, muscle and visceral nociceptive stimuli , 1993, Pain.

[6]  M. Urban,et al.  Supraspinal contributions to hyperalgesia. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[7]  J. Maisog,et al.  Pain intensity processing within the human brain: a bilateral, distributed mechanism. , 1999, Journal of neurophysiology.

[8]  F. Cerveró,et al.  Mechanisms of touch-evoked pain (allodynia): a new model , 1996, Pain.

[9]  A. Goodchild,et al.  A method for evoking physiological responses by stimulation of cell bodies, but not axons of passage, within localized regions of the central nervous system , 1982, Journal of Neuroscience Methods.

[10]  J. Dostrovsky,et al.  Phantom sensations generated by thalamic microstimulation , 1998, Nature.

[11]  H. You,et al.  Sex-related differences in descending norepinephrine and serotonin controls of spinal withdrawal reflex during intramuscular saline induced muscle nociception in rats , 2011, Experimental Neurology.

[12]  F. McGlone,et al.  The cutaneous sensory system , 2010, Neuroscience & Biobehavioral Reviews.

[13]  James N. Campbell,et al.  Peripheral and central mechanisms of cutaneous hyperalgesia , 1992, Progress in Neurobiology.

[14]  François Mauguière,et al.  Thalamic thermo-algesic transmission: ventral posterior (VP) complex versus VMpo in the light of a thalamic infarct with central pain , 2005, Pain.

[15]  L. Arendt-Nielsen,et al.  Endogenous descending modulation: spatiotemporal effect of dynamic imbalance between descending facilitation and inhibition of nociception , 2010, The Journal of physiology.

[16]  L. Monconduit,et al.  Ventromedial Thalamic Neurons Convey Nociceptive Signals from the Whole Body Surface to the Dorsolateral Neocortex , 1999, The Journal of Neuroscience.

[17]  G. Paxinos,et al.  The Rat Brain in Stereotaxic Coordinates , 1983 .

[18]  L. Arendt-Nielsen,et al.  Simultaneous recordings of wind-up of paired spinal dorsal horn nociceptive neuron and nociceptive flexion reflex in rats , 2003, Brain Research.

[19]  A. Pertovaara A Neuronal Correlate of Secondary Hyperalgesia in the Rat Spinal Dorsal Horn Is Submodality Selective and Facilitated by Supraspinal Influence , 1998, Experimental Neurology.

[20]  P. Wall,et al.  Does the right side know what the left is doing? , 1999, Trends in Neurosciences.

[21]  K. Krnjević,et al.  The action of gamma-aminobutyric acid on cortical neurones. , 1967, Experimental brain research.

[22]  B. Shyu,et al.  BOLD response to direct thalamic stimulation reveals a functional connection between the medial thalamus and the anterior cingulate cortex in the rat , 2004, Magnetic resonance in medicine.

[23]  M. Bushnell,et al.  A thalamic nucleus specific for pain and temperature sensation , 1994, Nature.

[24]  J. Dostrovsky,et al.  5.43 – The Thalamus and Nociceptive Processing , 2008 .

[25]  M. H. Evans,et al.  Measurement of current spread from microelectrodes when stimulating within the nervous system , 1976, Experimental Brain Research.

[26]  Susan Schwartz,et al.  The action of γ-Aminobutyric acid on cortical neurones , 2004, Experimental Brain Research.

[27]  C. Woolf Evidence for a central component of post-injury pain hypersensitivity , 1983, Nature.

[28]  Megan L Uhelski,et al.  Examining the role of the medial thalamus in modulating the affective dimension of pain , 2008, Brain Research.