Brain pain pathways

Describe the pain pathway and the role that each stimulated region of the brain plays in the response to pain... 

Figure 8.1 The pain pathway. The pain signal is transmitted to several regions of the brain, including the thalamus reticular formation hypothalamus limbic system and somatosensory cortex. Each region carries out a specific aspect of the response to pain.

Opioids basically exert their analgesic effects by inhibiting synaptic transmission in key pain pathways in the spinal cord and brain. This inhibitory effect is mediated by opioid receptors that are located on both presynaptic and postsynaptic membranes of pain-mediating synapses (Fig. 14—2). In the spinal cord, for example, receptors are located on the presynaptic terminals of primary (first-order) nociceptive afferents, and when bound by opioids, they directly decrease the release of pain-mediating transmitters such as substance P.35,38 Opioid drug-receptor interactions also take place on the postsynaptic membrane of the secondary afferent neuron—that is, the second-order nociceptive afferent neuron in the spinal cord.19,33 When stimulated, these receptors also inhibit pain transmission by hyperpolarizing the postsynaptic neuron.19... 

Opioids therefore inhibit synaptic transmission by decreasing neurotransmitter release from the presynaptic terminal and by decreasing excitable (hyperpolarizing) postsynaptic neurons within key pain pathways in the spinal cord and brain. Again, these synaptic effects can either limit the transmission of painful stim-... 

Serotonin Usually inhibitory helps control mood, influences sleep, and inhibits pain pathways in the spinal cord. Secreted by subcortical structures into hypothalamus, brain, and spinal cord. There are many subtypes of serotonin receptors. Diffuse and widespread symptoms depression, headache, diarrhea, constipation, sexual dysfunction, and other medical symptoms. The selective serotonin reuptake inhibitors (SSRIs), the most commonly used antidepressants, work specifically on this neurotransmitter system. 

The above discrepancies seem to be due mainly to the stringencies of the end-points in each test. However, one can also doubt the applicability of these tests for cannabinoids. These tests were developed for opiates and may not necessarily parallel and be fully relevant to THC activity in man. Indeed, recent work on electrodes implanted into several distinct brain areas of the rat led to the conclusion that the apparent analgesia produced by the cannabinoids is more related to their disruption of discharge in response to some synthetic impact rather than to a depression of pain pathways [130]. The question whether cannabinoids cause analgesia by interference with pain reception or with pain perception is still unresolved. 

Almeida T F, Roizenblatt S, Tufik S (2004). Afferent pain pathways A neuroanatomi-cal review. Brain Res. 1000 40-56. 

In addition to its central stimulation of I1-IBS and Q2-adrenoceptors (20,21), clonidine (as well as other Q2-adrenergic agonists), when administered epidurally, produces analgesia by stimulation of spinal a2-adrenoceptors, inhibiting sympathetically mediated pain pathways that are activated by nociceptive stimuli, thus preventing transmission of pain signals to the brain (9). Activation of a2-adrenoceptors also apparently stimulates acetylcholine release and inhibits... 

Divalent nations appear to be involved in the pain pathway and magnesium sulfate ean potentiate the opioid analgesic effect, possibly by antagonism of A -methyl-D-aspartate receptor ion channels. It has been suggested that as magnesium ions do not easily cross the blood brain bar-... 

At the same time it promotes a discharge of epinephrine from the adrenal medulla, as well as discharge of catecholamines from sympathetic nerve endings, resulting in activation of spinal cord and brain descending inhibitory pain pathways. 

The ascending pain pathway commences at the afferent nociceptive fibres which send information to the brain via the spinal cord where they form synapses with its dorsal horn where pain is comprehended. 

The triptans are considered specific therapies in that they target the pathophysiology underlying migraine.33 They abort headache through beneficial effects on neuronal imbalances.11 Triptans inhibit neurotransmission in the trigeminal complex and activate serotonin lb/Id pathways that modulate nociception in the brain stem. They also decrease the release of vasoactive peptides leading to vascular reactivity and pain.34 Triptans are a welcome addition to the therapeutic armamentarium in that they are available in intranasal, subcutaneous, and oral... 

The second-order sensory neuron transmits impulses ultimately to the left side of the brain. This permits the awareness of pain, identification of its source, and, if necessary, postural adjustment. As discussed, impulses in this pathway do not play a role in the reflex per se. 

Stimulation of a nociceptor in the periphery of the body elicits action potentials in the first-order neuron, which transmits the signal to the second-order neuron in the dorsal horn of the spinal cord. From the spinal cord, the signal is transmitted to several regions of the brain. The most prominent ascending nociceptive pathway is the spinothalamic tract. Axons of the second-order sensory neurons project to the contralateral (opposite) side of the spinal cord and ascend in the white matter, terminating in the thalamus (see Figure 8.1). The thalamus contributes to the basic sensation or awareness of pain only it cannot determine the source of the painful stimulus. 

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