Pain Control Mechanisms (PDF)

13 Pain control mechanisms ILOs By the end of this lecture, students will be able to 1. Discuss spinal cord role in the gating of nociceptive transmission. 2. Interpret how nociceptive transmission can be modulated 3. Discuss role of endorphins versus other transmitters...

13 Pain control mechanisms ILOs By the end of this lecture, students will be able to 1. Discuss spinal cord role in the gating of nociceptive transmission. 2. Interpret how nociceptive transmission can be modulated 3. Discuss role of endorphins versus other transmitters in central control of pain 4. Identify location and functions of the endogenous analgesic centers. The transmission of information from primary afferents to secondary neurones in the spinal cord is not only a passive process but is a dynamic process including excitation, inhibition and modulation. Neurones in the superficial dorsal horn are subject to modulation that GATES the flow of information to the CNS. These descending influences on posterior horn neurons can be both inhibitory and facilitatory. The balance between inhibition and facilitation can be altered to meet different behavioral, emotional, and pathophysiological needs GATE CONTROL THEORY Proposed by Patrick Wall and Ronald Melzack. This theory states that pain is a function of the balance between the information traveling into the spinal cord through large (non-nociceptive) nerve fibres and information travelling into the spinal cord through small (nociceptive) nerve fibres. Without any stimulation, both sets of nerve fibres are inactive and the inhibitory neurone (I) blocks the signal in the projection neurone (P) that connects to the brain. The gate is ‘closed’, and therefore no pain is sensed. With non-painful stimulation, large nerve fibres are activated. This activates P, but it also activates I, which then blocks the signal in P, that connects to the brain. As the gate is ‘closed’, no stimulation is perceived by the brain. With noxious stimulation, nociceptive fibres become active. They activate P and, , block I (it is now known that this does not occur). Since activity of the inhibitory neurone is blocked, it cannot block the output of the projection neurone that connects with the brain. Therefore, if the relative amount of activity is greater in large nerve fibres, there should be little or no pain. However, if there is more activity in small nerve fibres, then pain takes place, because the gate is ‘open’. Rubbing the head or shin stimulates the non-nociceptive afferents that send impulses into the spinal cord. This phenomenon can be explained by the gate theory, where the inhibitory interneurones are activated either directly or indirectly by stimulation of these afferents from the skin that would then block the projection neurone and therefore block the pain. This may explain why counter- stimulation techniques are sometimes effective at relieving pain. Fig. 1 Gate control theory Supraspinal (descending) analgesia It is a mechanism by which the brain can reduce pain. It uses feedback loops that involve several different nuclei in the brainstem reticular formation. Areas of the brainstem that are involved in reducing pain are the periaqueductal gray (PAG), the nucleus raphe magnus (NRM) and the locus coeruleus (LC). The PAG is very important in the control of pain. This region surrounds the cerebral aqueduct in the midbrain. Neurosurgeons can implant stimulating electrodes near the PAG of intractable pain patients. The PAG contains enkephalin-rich neurones that excite the NRM and/or LC neurones. This allows PAG (anti- nociceptor) neurones to excite the amine-containing cells in NRM and LC that in turn project to the spinal cord to block pain transmission by dorsal horn cells. Stimulation of the raphe nuclei produces a powerful analgesia and it is thought that the 5-HT released by this stimulation activates the inhibitory interneurones even more powerfully than noradrenaline (from LC) and thus blocks pain transmission. The descending serotonergic and noradrenergic axons induce release of enkephalin from certain dorsal horn interneurons as well as activating some GABAergic inhibitory interneurones. These interneurons can act both postsynaptically on projection cells by causing hyperpolarization and opening potassium channels or presynaptically via closing calcium channels and inhibition of neurotransmitter release from primary afferent terminals. Arousal (stress) analgesia Recent work has clarified the mechanisms involved in the analgesia seen during intense excitement or arousal. During arousal, the sympathetic nervous system is active in the body. Sympathetic fibres activate the slow pain pathways, whose axons ascend to activate noradrenergic cells in the locus coeruleus. Noradrenergic axons project back down to the spinal cord neurons which can block pain transmission through different inhibitory interneurons. Therefore, agents that increase noradrenergic transmission have analgesic potential. Additionally, activity from autonomic brain areas such as the hypothalamus or the amygdala stimulates the PAG to induce analgesia. This is involved in the fight or flight reaction that produces hypoalgesia in life-threatening situations, e.g. on battlefields. Fig. 2. Supraspinal (descending) analgesia