Pain mediator substance

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... 

Pain. Prostaglandins appear to help mediate painful stimuli in a variety of conditions (including inflammation). The compounds do not usually produce pain directly but are believed to increase the sensitivity of pain receptors to mechanical pressure and the effects of other pain-producing substances such as bradykinin.73... 

An undecapeptide called substance P is an excitatory neurotransmitter which appears to have a role in pain mediation and is worthy of further study. 

Substance P (SP), which is the undecapeptide involved in pain mediation (Chapter 5), even though it is not fully characterized due to lack of specific antagonists, is considered an excitatory neurotransmitter. It occurs in all brain areas and the spinal cord. Neuroactive peptides are frequently found to coexist in amino acid or monoamine secreting neurons (e.g., SP in cholinergic and serotoninergic fibers, and somatostin with GABA). 

Substance P is an arteriolar vasodilator that is also a pain-mediating neurotransmitter. The answer is (I),... 

Histamine also induces antinociceptive (i.e. pain-relieving) responses in animals after microinjection into several brain regions [73, 74]. H, and H2 mechanisms are significant and both neuronal and humoral mechanisms may be involved. Brain H2 receptors appear to mediate some forms of endogenous analgesic responses, especially those elicited by exposure to stressors [75]. Many of the modulatory actions of histamine discussed above appear to be activated as part of stress responses. For reasons that remain unclear, histamine releasers, such as thioperamide, show only mild, biphasic antinociceptive actions, even though histamine is a potent and effective analgesic substance. Outside the brain, both H and H3 receptors exist on certain types of sensory nerves and activation of these receptors promotes and inhibits, respectively, peripheral nerve transmission related to pain and/or inflammation [76,77]. 

Capsaicin (Zostrix) is approved for the relief of pain following herpes zoster infection (postherpetic neuralgia). The drug depletes neurons of substance P, an endogenous neuropeptide that may mediate cutaneous pain. It is applied to affected skin after open lesions have healed. Local irritation is common. 

Schematic diagram of a primary afferent neuron mediating pain, its synapse with a secondary afferent in the spinal cord, and the targets for local pain control. The primary afferent neuron cell body is not shown. At least three nociceptors are recognized acid, injury, and heat receptors. The nerve ending also bears opioid receptors, which can inhibit action potential generation. The axon bears sodium channels and potassium channels (not shown), which are essential for action potential propagation. Synaptic transmission involves release of substance P, a neuropeptide (NP) and glutamate and activation of their receptors on the secondary neuron. Alpha2 adrenoceptors and opioid receptors modulate the transmission process.

Opiates act on a variety of receptors. The three most important subtypes are the mu, delta, and kappa opiate receptors (Fig. 13—25). The brain makes its own endogenous opiate-like substances, sometimes referred to as the brain s own morphine. They are peptides derived from precursor proteins called pro-opiomelanocortin (POMC), proenkephalin, and prodynorphin. Parts of these precursor proteins are cleaved off to form endorphins or enkephalins, stored in opiate neurons, and presumably released during neurotransmission to mediate endogenous opiate-like actions (Fig. 13-25). However, the precise number and function of endogenous opiates and their receptors and their role in pain relief and other central nervous system (CNS) actions remain largely unknown. 

Substance P Pathways in spinal cord and brain that mediate painful stimuli Excitation... 

This pungent product is responsible for the intense irritant effects of topical Capsicum preparations. Repeated application of capsaicin can deplete and prevent reaccumulation of substance P, an endogenous mediator of pain impulses from the periphery to the CNS. Since the early 1990s, capsaicin cream has been available in the U.S. as an approved drug for relief of postherpetic neuralgia and pain due to diabetic neuropathy and osteoarthritis. 

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