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Unformatted text preview: Pain • Submodality of the sense of touch, warns of injury and things that should be avoided. • h;p://english.pravda.ru/science/ 19/94/377/14726_pain.html • Somehow more subjecGve than the other senses. The same sGmulus can produce diﬀerent responses in diﬀerent individuals, or in the same individual in diﬀerent circumstances. nociceptors • Transfer informaGon about pain. • Three major classes of nociceptors: Aδ mechanosensiGve nociceptors, Aδ mechanothermal nociceptors, and polymodal nociceptors. • Aδ mechanosensiGve nociceptors‐acGvated by intense pressure, are lightly myelinated and have speeds of 5‐30 m/s. • Aδ mechanothermal nociceptors are acGvated by very hot or very cold temperatures. Are also lightly myelinated. • Polymodal nociceptors (C ﬁbers) respond to temperature,pressure, or chemicals, are unmyelinated and conduct at speeds of 1m/s. • Aδ and C ﬁbers also have cold temperature gated ion channels. Because they are located in same neuron, when they ﬁre they are perceived as pain. • Pain receptor recepGve ﬁelds are generally pre;y large presumably because the detecGon of pain is more important than its exact locaGon. Pain involves specialized neurons not just extra sGmulaGon of touch receptors. arrangement for transcutaneous nerve recording. nociceptor doesn’t ﬁre unGl pain is felt. Other thermorecptors ﬁre at all temps and at about the same frequency How do we detect pain? • A family of Ion channel receptors have been found that open in response to heat as well as capsaicin called TRP (transient receptor potenGal) channels. • Structurally resemble voltage‐gated K+ channels, having 6 transmembrane domains that make a pore. • When open allows Ca and Na in to generate the acGon potenGal. Heat gated ion channels • Capsaicin receptors are nonselec2ve ca2on channels opened by heat, low pH, and capsaicin (the hot in hot peppers). • Mice without VR1 have impaired sensi2vity to pain. Can drink capsaicin as if it were water. Nociceptors • The ﬁgure compares the ac2va2on of VR1 channels by pure capsaicin and extracts of various peppers. Nature 1997 Oct 23;389(6653):816-24 Two types of pain • ﬁrst pain (sharp), Aδ ﬁbers • second pain (dull, longer lasGng) C‐ﬁbers Two Categories of Pain PercepGon selecGve block of either Aδ or C ﬁbers hyperalgesia • Enhanced sensiGvity and responsivity to sGmulaGon of the area around the damaged Gssue. SGmuli that would not ordinarily be perceived as pain now is. For example ader a sunburn a normal shower now feels painful. • Due to the release of stuﬀ from the damaged cells, such as prostaglandins, bradykinin, histamine, serotonin, ATP can increase the sensiGvity of nociceptors by interacGng with the channel (directly or indirectly) and making it open easier, or by interacGng with other receptors on nocicepGve ﬁbers to potenGate acGvity of TRP channels. • Aspirin and ibuprofen inhibits cyclooxygenases, necessary for prostaglandin synthesis. • Shows that pain and injury are inter‐related Correlation between the perception of pain in a human subject and impulse firing in a monkey C multimodal heat receptor under normal conditions and during hyperalgesia. Lots of things can modify pain sensiGvity Rang et al Pharmacology 5E (2003) Nociceptor terminals, ion channels, receptors and inﬂammatory mediators – targets for analgesia Rang et al Pharmacology 5E (2003)
The spinothalamic tract • Cell bodies found in the most lateral parts of the dorsal roots, but not discretely localized. • Innervate neurons in the dorsal horn of the spinal cord. Some of these neurons project within the spinal cord. These are important for reﬂex behaviors. • Others project axons cross the midline in the same segment and then go up to the brain. Major Pathways for Pain (and Temperature) SensaGon nocicepGve components of the thalamus • Pain and temp go to VPM and VPL nuclei just like the mechanosensory axons. • VPM from the face, VPL from the body • presumably responsible for our ability to locate a pain with respect to body posiGon. Major Pathways for Pain (and Temperature) SensaGon Pathways for Pain (and Temperature) SensaGon of the face Cortex • VPM and VPL neurons project to SI. These neurons have small recepGve ﬁelds and are likely used to locate where the pain is. But are not responsible for dull aches that are associated with chronic pain as ablaGon does not reduce pain. • There are also direct projecGons from the thalamus to the reGcular formaGon (in medulla), and the interlaminar nuclei of the thalamus. These neurons project to areas of the limbic system and are responsible for the emoGonal aspects of pain. pain vs touch • 2nd order mechanosensory axons cross at the level of the medulla but 2nd pain axons cross at about the segment their cell bodies are in. • If there is a damage on one side of the spinal cord, below the injury site, there would be no sense of touch on the same side and no sense of pain on the contralateral side. Spinothalamic Tract also called anterolateral column part of the ventral column • Note where somatosensory tracts cross over. • Touch and pain are on opposite sides below medulla • Touch and pain are on the same side above medulla touch is faster than pain Dorsal roots 1. Dorsal column 2. Lateral column 3. Ventral column DRG 2 1 3 Ventral roots Pa;ern of "Dissociated" Sensory Loss Following a Spinal Cord HemisecGon Referred pain Few if any neurons in dorsal horn are specialized solely for the transmission of visceral pain. It is conveyed to brain via dorsal horn neurons that also get inputs from skin. Therefore a person may feel pain at a site completely diﬀerent than its source. Pain percepGon is subjecGve • Pain is somewhat subjecGve. Depends on context. Soldiers wounded in ba;le feel less pain than if one gets the same injury at home. • Placebo aﬀects. • Rubbing the site of injury can make pain less severe. • There is a descending pain pathway that can impinge on the dorsal horn to quiet neurons. Gate theory of pain Axons from neurons with mechanoreceptors synapse onto inhibitory interneurons in spine AcGvaGon of inhibitory interneurons dampens pain signal Direct electrical sGmulaGon of the brain produces analgesia • The observaGon is that sGmulaGon of periaqueductal gray ma;er (in midbrain) or rostral medulla reduces pain. • sGmulaGon only reduces pain sensaGon, animal sGll responds to touch, temp etc, just feels less pain. • These areas are part of a descending pathway that modulates pain. Cortex and hypothalamus project to periaqueductal grey ma;er‐projects to nuclei in the medulla (Raphe nuclei, reGcular formaGon), projects to dorsal horn, where they can inhibit ascending pain ﬁbers. The Descending Systems that Modulate the Transmission of Ascending Pain Signals • Descending pathways from cortex and hypothalamus… The Descending Systems that Modulate the Transmission of Ascending Pain Signals • through periaqueductal gray rostral medulla reduce ac2vity in spinothalamic tract. • Reduc2on of ac2vity in the spinothalamic tract. opioids • Opioid receptors (metabotropic) are expressed in the areas of descending pain pathway (also expressed in other areas, such as muscles of the bowel and anal sphincter). • Ligands‐ enkephalins, endorphins, and dynorphin. Found in all descending pain areas. • Opiate antagonist naloxone blocks sGmulaGon produced analgesia as well as morphine‐induced analgesia. Suggests that they are the same thing. • Opioids decrease the chance that a nociceptor will ﬁre, cause inhibiGon. Opioid pepGdes hyperpolarize cells to decrease acGon potenGal ﬁring Placebo Eﬀect • Sugar pills can reduce percepGon of pain. • The eﬀect can be blocked by naloxone, a compeGGve antagonist of opioid receptors. • The placebo eﬀect is based on a biochemical change in the brain. As are all percepGons. Endogenous Opioids • PN10T20.JPG ...
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