Substance P: Difference between revisions

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[[File:Substance P.svg|thumbnail|Substance P.]]

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==Role in pain perception and interaction with opioids==

The most investigated role of SP has been in the perception of pain, although its effects seem to be more complex than simply "more means more pain." SP is abundant in the spinal cord, where it is synthesized in the ~~spina~~ ganglia and transported centrally to the substantia gelatinosa and peripherally to nerve endings in many areas of the human body.<ref name="pain" /> Nociception is usually mediated by C and Aδ fibers which are activated by painful stimuli. SP performs a central role in this pathway. Aβ fibers normally send innocent tactile sensations from the periphery to the central nervous system, but inflammation can cause hypersensitivity to pain, and it has been demonstrated that a subset of Aβ fibers will switch their phenotype to one that expresses SP, and thus become more pain-like, in the presence of inflammation.<ref>Inflammatory pain hypersensitivity mediated by phenotypic switch in myelinated primary sensory neurons | http://www.nature.com/nature/journal/v384/n6607/abs/384360a0.html</ref>

The most investigated role of SP has been in the perception of pain, although its effects seem to be more complex than simply "more means more pain." SP is abundant in the spinal cord, where it is synthesized in the spinal ganglia and transported centrally to the substantia gelatinosa and peripherally to nerve endings in many areas of the human body.<ref name="pain" /> Nociception is usually mediated by C and Aδ fibers which are activated by painful stimuli. SP performs a central role in this pathway. Aβ fibers normally send innocent tactile sensations from the periphery to the central nervous system, but inflammation can cause hypersensitivity to pain, and it has been demonstrated that a subset of Aβ fibers will switch their phenotype to one that expresses SP, and thus become more pain-like, in the presence of inflammation.<ref>Inflammatory pain hypersensitivity mediated by phenotypic switch in myelinated primary sensory neurons | http://www.nature.com/nature/journal/v384/n6607/abs/384360a0.html</ref>

A number of NK1 receptor antagonists have been developed and tested for analgesic purposes, with limited success.<ref name="analgesia">NK1 (substance P) receptor antagonists – why are they not analgesic in humans?| http://www.sciencedirect.com/science/article/pii/S0165614700015029</ref> Although preclinical data from animal experiments indicated that NK1 antagonists should produce pain relief in humans, the antagonists showed NK1 antagonists to be for the most part completely ineffective as analgesics in humans. This despite the fact that they showed a similar effect profile in animal tests to that of established analgesics like non-steroidal anti-inflammatory drugs (NSAIDs). In addition, the same animal models translated successfully into clinically effective antiemetic drugs. There could be a number of explanations for this; the simplest one being that pain perception is a complex phenomenon in which no one receptor or neurotransmitter is solely responsible. Others include differences in the pharmacology of NKAs in animals and humans, the role of NK2 and NK3 receptors, and the blurring of the lines between stress and pain, as Substance P is also heightened in stressful situations.

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 [[File:Substance P.svg|thumbnail|Substance P.]]
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 ==Role in pain perception and interaction with opioids==
-The most investigated role of SP has been in the perception of pain, although its effects seem to be more complex than simply "more means more pain." SP is abundant in the spinal cord, where it is synthesized in the spina ganglia and transported centrally to the substantia gelatinosa and peripherally to nerve endings in many areas of the human body.<ref name="pain" /> Nociception is usually mediated by C and Aδ fibers which are activated by painful stimuli. SP performs a central role in this pathway. Aβ fibers normally send innocent tactile sensations from the periphery to the central nervous system, but inflammation can cause hypersensitivity to pain, and it has been demonstrated that a subset of Aβ fibers will switch their phenotype to one that expresses SP, and thus become more pain-like, in the presence of inflammation.<ref>Inflammatory pain hypersensitivity mediated by phenotypic switch in myelinated primary sensory neurons | http://www.nature.com/nature/journal/v384/n6607/abs/384360a0.html</ref>
+The most investigated role of SP has been in the perception of pain, although its effects seem to be more complex than simply "more means more pain." SP is abundant in the spinal cord, where it is synthesized in the spinal ganglia and transported centrally to the substantia gelatinosa and peripherally to nerve endings in many areas of the human body.<ref name="pain" /> Nociception is usually mediated by C and Aδ fibers which are activated by painful stimuli. SP performs a central role in this pathway. Aβ fibers normally send innocent tactile sensations from the periphery to the central nervous system, but inflammation can cause hypersensitivity to pain, and it has been demonstrated that a subset of Aβ fibers will switch their phenotype to one that expresses SP, and thus become more pain-like, in the presence of inflammation.<ref>Inflammatory pain hypersensitivity mediated by phenotypic switch in myelinated primary sensory neurons | http://www.nature.com/nature/journal/v384/n6607/abs/384360a0.html</ref>
 A number of NK1 receptor antagonists have been developed and tested for analgesic purposes, with limited success.<ref name="analgesia">NK1 (substance P) receptor antagonists – why are they not analgesic in humans?| http://www.sciencedirect.com/science/article/pii/S0165614700015029</ref> Although preclinical data from animal experiments indicated that NK1 antagonists should produce pain relief in humans, the antagonists showed NK1 antagonists to be for the most part completely ineffective as analgesics in humans. This despite the fact that they showed a similar effect profile in animal tests to that of established analgesics like non-steroidal anti-inflammatory drugs (NSAIDs). In addition, the same animal models translated successfully into clinically effective antiemetic drugs. There could be a number of explanations for this; the simplest one being that pain perception is a complex phenomenon in which no one receptor or neurotransmitter is solely responsible. Others include differences in the pharmacology of NKAs in animals and humans, the role of NK2 and NK3 receptors, and the blurring of the lines between stress and pain, as Substance P is also heightened in stressful situations.