Anatomy of the nervous system

Pain is an unpleasant experience which results from both physical and psychological responses to injury. A complex set of pathways transmits pain messages from the periphery to the central nervous system, where control occurs from higher centres. Primary afferent pain fibres synapse with second-order neurons in the dorsal horn of the spinal cord. Ascending spinothalamic and spinoreticular tracts convey pain up to the brain, where pain signals are processed by the thalamus and sent to the cortex. Descending tracts, via the midbrain periaquaductal grey and nucleus raphe magnus, have a role in pain modulation. When nerves are damaged, neuropathic pain results and various mechanisms have been proposed for how this takes place. These mechanisms involve both peripheral and central sensitization.

1986

These findings have supplemented and refined a wealth of anatomic and physiological information on synaptic interactions within the dorsal horn that are relevant to pain coding (see Willis, Chapter 11; Cervera, Chapter 9). The weakest link in this intense effort to understand the totality of influences on pain transmission within the spinal cord (Kerr, 1975b) has been the behavioral analysis of pain sensitivity in human patients and laboratory animals (primarily rats, cats, and monkeys).

Journal of Clinical Neurophysiology, 1997

We review many of the recent findings concerning mechanisms and pathways for pain and its modulation, emphasizing sensitization and the modulation of nociceptors and of dorsal horn nociceptive neurons. We describe the organization of several ascending nociceptive pathways, including the spinothalamic, spinomesencephalic, spinoreticular, spinolimbic, spinocervical, and postsynaptic dorsal column pathways in some detail and discuss nociceptive processing in the thalamus and cerebral cortex. Structures involved in the descending analgesia systems, including the periaqueductal gray, locus ceruleus, and parabrachial area, nucleus raphe magnus, reticular formation, anterior pretectal nucleus, thalamus and cerebral cortex, and several components of the limbic system are described and the pathways and neurotransmitters utilized are mentioned. Finally, we speculate on possible fruitful lines of research that might lead to improvements in therapy for pain.

The transmission of pain from peripheral pain receptors to the brain is mediated by several ascending nociceptive pathways, including the spinothalamic, spinomesencephalic, spinoreticular, spinolimbic, spinocervical, and dorsal column pathways (for a detailed review, see the article by Willis and Westlund [1]). Nociceptive projection neurons in the spinal cord transmit information to a number of regions of the brain stem and diencephalon, including the thalamus, periaqueductal gray (PAG), parabrachial region, and bulbar reticular formation, as well as to limbic structures in the hypothalamus, amygdaloid nucleus, septal nucleus, and other sites . Much of the nociceptive processing involving the cognitive and affective components of pain is mediated by higher centers, such as the limbic system, thalamus, and neocortex. Several central structures are also involved in the descending analgesia systems, including the neocortex, limbic system, thalamus, PAG, locus ceruleus, parabrachial area, nucleus raphe magnus (NRM), reticular formation, and anterior pretectal nucleus.

Experimental Physiology, 2002

Disease-a-Month, 2013

Pain occurring at the end of life is often a complex amalgam of symptoms that arise from neuropathic, somatic, and visceral pain syndromes. Likewise, the stimuli from which the pain syndromes originate are complex and may include inflammatory, neuropathic, and ischemic components. 1 The palliative management of pain is further complicated by nociceptor sensitization that often occurs in chronic pain syndromes 1-3 and by the affective components involved. Although neural plasticity and sensitization obfuscate the direct etiologies of chronic pain, it is ultimately pain signal transduction that underlies chronic pain; thus an understanding of acute pain signaling pathways is critical in the provision of effective palliative pain management. Pain itself, like joy or pleasure, initiates from within. It is the end result of central processing of sensory stimuli. Sensations of acute pain occur when stimuli of sufficient intensity lead to the depolarization of high-threshold nociceptors. Impulses generated from exposure to heat, chemical injury, and mechanical stimuli are transduced into electrical signals that are carried to the dorsal horn of the spinal cord, where the primary neurons form synapses with secondary neurons that ascend to the central nervous system (CNS). Lightly myelinated Aδ fibers rapidly carry signals that relay and pinpoint the topographic origins of sharp pain, while unmyelinated C-fibers more slowly carry diffuse signals that relay burning or dull aching sensations. Normally, large myelinated Aα and Aβ very rapidly conduct non-noxious signals (e.g., vibration and touch); signaling through these fibers may become deranged during inflammation or after healing of traumatic tissues, leading to aberrant pain sensations. 4 In the dorsal horn, the primary neurons synapse with secondary neurons and interneurons located in different layers of the dorsal horn. Secondary neurons with cell bodies that originate in Rexed layer I and II are specific for noxious stimulation of mechanical and thermal origin; these are the neurons that comprise the neospinothalamic tract, which transmits topographic and intensity-related information to the cortex for rapid response. Secondary neurons whose cell bodies lie in Rexed area V are known as non-specific, convergent, polymodal, or widedynamic-range neurons because they can be activated both by fibers that carry painful stimuli of tactile, muscular, or visceral origin and by fibers that carry non-noxious stimuli. These secondary Contents lists available at ScienceDirect

NeuroImage, 2005

We measured, with whole-scalp magnetoencephalography, evoked fields from 10 healthy subjects to 1-ms thulium-laser stimuli that selectively activated nociceptive nerve fibers. The stimuli were delivered to the dorsum of the subject's left hand. The earliest cortical responses peaked at 165 F 7 ms, agreeing with the conduction velocity of Ay-fibers. To stimulate unmyelinated C-fibers, we modified the method of Bragard et al. . Direct isolation of ultra-late (C-fibre) evoked brain potentials by CO 2 laser stimulation of tiny cutaneous surface areas in man. Neurosci. Lett. 209,[81][82][83][84], by decreasing the total energy of the laser beam and by restricting the size of the stimulated skin area to 0.2-0.3 mm 2 . The earliest cortical responses to these stimuli peaked at 811 F 14 ms. Bilateral activation of the SII cortices was detected in all 10 subjects to Ay and in 8 subjects to C stimuli, emphasizing the importance of the SII cortex in processing of pain. Additional activation was observed in the posterior parietal cortex (PPC), probably related to sensorimotor coordination targeted to produce precise motor acts that reduce or prevent the pain; the PPC activation may have been accentuated by the required continuous evaluation of the perceived pain. In contrast to some earlier studies, we did not observe activation of the primary somatosensory cortex (SI). Additional activations to both types of stimuli were detected in the cingulate cortex (three subjects) and in the bilateral insular cortex (two subjects). These results implicate that the nociceptive inputs mediated by the Ay-and C-fibers are processed in a common cortical network in different time windows. Reliable temporospatial characterization of cortical responses to first and second pain offers a unique tool for basic and clinical neuroscience to study the two distinctive pain fiber systems at cortical level. D

The central nervous system includes the brain and spinal cord. The brain and spinal cord are protected by bony structures, membranes, and fluid. The brain is held in the cranial cavity of the skull and it consists of the cerebrum, cerebellum, and the brain stem. The nerves involved are cranial nerves and spinal nerves.

Pain, 1996

The involvement of the dorsal part of the caudal medulla in both the transmission and modulation of pain is supported by recent electrophysiological and anatomical data. In this review, we analyse the features of a well-delimited area within the caudal-most aspect of the medulla, the subnucleus reticularis dorsalis (SRD) which plays a specific role in processing cutaneous and vi~ceral nociceptive inputs. From a general viewpoint, the reciprocal connections between the caudal medulla and spinal cord suggest that this area is an important link in feedback loops which regulate spinal outflow. Moreover, the existence of SRD-thalamic connections put a new light on the role of spino-reticulo-thalamic circuits in pain transmission.