Receptors, pain

The mechanism of action of these anesthetics involves the blockade of sodium channels in the membrane of the second-order sensory neuron. The binding site for these anesthetics is on a subunit of the sodium channel located near the internal surface of the cell membrane. Therefore, the agent must enter the neuron in order to block the sodium channel effectively. Without the influx of sodium, neurons cannot depolarize and generate an action potential, so the second-order sensory neuron cannot be stimulated by impulses elicited by pain receptors associated with the first-order sensory neuron. In other words, the pain signal is effectively interrupted at the level of the spinal cord and does not travel any higher in the CNS. In this way, the brain does not perceive pain. 

Pain receptors also influence the medullary respiratory center. Pain may cause a reflex increase in ventilation in the form of a "gasp." Somatic pain typically causes hyperpnea and visceral pain typically causes apnea, or decreased ventilation. 

Signals from pain receptors are transmitted to the brain where they are processed in the thalamus and then passed on to the sensory cortex where the sensation of pain originates. Receptors for endorphins (and for the opiates) are abundant in these regions and it is likely that a natural role of endorphins is to interfere with the transmission of impulses through these regions. The opiates appear to do the same, acting not so much to alter the pain threshold but altering the patient s attitude to pain. 

Although most consumers appreciate the fieriness of chile, capsaicinoids are not perceived through odor or taste receptors but through the nociceptive pain receptors described earlier. The compounds in chile fruit that create the flavor and aroma are produced in the fruit wall. Buttery et al. [90] generated vacuum steam distilled oil from green bell pepper macerate, with well over 40 peaks on subsequent GC/MS analysis. Of these peaks, the major flavor compound associated with bell pepper aroma was 2-methoxy-3-isobutylpyrazine (Fig. 8.1). They also reported several monoterpenoids in abundance, limonene, trans- 3-ocimene, and linalool as well as other aliphatic aldehydes and ketones. The flavor composition of dried red bell pepper powder (sweet paprika) extracted with ether identified 44 key peaks by GC/MS [91]. In these dried samples the key compounds were P-ionone and several furanones. The post-harvest processing and the different fruit maturities as well as possible varietal differences are all causes for the different aromatic profiles. 

Apart from their anti-inflammatory activity the NSAIDs also show, dependent on the condition and the type of pain, considerable analgesic efficacy. In some forms of postoperative pain the NSAID s can be as efficacious as opioids, especially when prostaglandins, bradykinin and histamine, which are released by inflammation, have caused sensitization of pain receptors to normally painless stimuli. In Table 4 some advantages and disadvantages of NSAID s and opioids are compared. Although analgesic effects at peripheral or central neurons cannot be excluded completely, most studies indicate that... 

The pain is mediated via pain receptors (nociceptors) from the damaged tissue. The pain signal... 

The peripheral component of their analgesic action is due to the inhibition of prostaglandin synthetase and thereby inhibiting the synthesis of prostaglandins (PGs) which sensitise the pain receptors to mechanical and chemical stimuli. Aspirin inhibits prostaglandin synthesis and blocks the sensitization of pain mechanism. 

EMLA applied to intact skin provides dermal analgesia by the release of lidocaine and prilocaine from the cream into the epidermal and dermal layers of the skin. There is cumulation of lidocaine and prilocaine in the vicinity of dermal pain receptors and nerve endings. The quality and duration of dermal analgesia depends primarily on the duration of application. EMLA should be applied 1-2 hours before the planned intervention, e.g. venepuncture, split skin harvesting. 

Pain receptors in the skin (cutaneous) and other tissues (non-cutaneous) are all free nerve endings. They are widespread in the superficial layers of the skin and in certain internal tissues such as the arterial walls and joints. Most other deep tissues contain few free nerve endings and so tissue damage there is more likely to cause a slow, chronic, dull ache rather than acute pain in these areas. 

Jancso, N. Desensitization with capsaicin and related acylamides as a tool for studying the function of pain receptors, edited by K. Lin, D. Armstrong, E.G. Prado, Pharmacology of Pain, 1968, Pergamon Press, Oxford, 33-55. 

Moncada S, Ferreira SH, Vane JR. Sensitization of pain receptors of dog knee joint by prostaglandins. In Robinson HJ, Vane JR, editors. Prostaglandin Synthetase Inhibitors. New York Raven Press, 1974 189. 

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... 

Recently fentanyl has been tested on AIDS patients. The drug is useful in blocking pain receptors, which helps patients cope with their pain. It also helps AZT to cross the blood-brain barrier. When used alone, AZT also has several side effects that early testing has shown to be reduced when fentanyl is added to the treatment. 

FIGURE 10.2 Pain receptor VRl(TRPVl) is localized in human epidermal keratinocytes. 

VR1 is a cation channel and originally it was discovered as a polymodal pain receptor in the nerve system.52 The role of VR1 in the epidermal keratinocytes has not been clarified. It might be associated with sensory perception of the skin. Temperature and osmotic pressure sensitive receptors are also found in the epidermal keratinocytes.53,54 Epidermal keratinocytes might play a crucial role as a sensor against environmental changes. 

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