Pain mediator histamine

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]. 

Binds to DNA and prevents separation of the helical strands Affects neuronal transmissions Binds to opiate receptors and blocks pain pathway Acts as central nervous system depressant Inhibits Na/K/ATPase, increases intracellular calcium, and increases ventricular contractibility Blocks the actions of histamine on Hi receptor Blocks ai-adrenergic receptor, resulting in decreased blood pressure Inhibits reuptake of 5-hydroxytryptamine (serotonin) into central nervous system neurons Inhibits cyclooxygenase, inhibition of inflammatory mediators Inhibits replication of viruses or tumor cells Inhibits HIV reverse transcriptase and DNA polymerase Antagonizes histamine effects... 

Histamine is a powerful stimulant of nerve endings, both motor and sensory nerves (32). Its stimulation is important in producing pain and itching, which are important components of the urticarial response and reactions to insect stings ( ). This effect is mediated through Hj receptors. Such nerve stimulation might conceivably be important in the initiation of the emetic response. 

Postsynaptic Hj- and Hj-receptors are responsible for a variety of processes in the CNS. Hi-receptors mediate the maintenance of wakeful states, while Hj- and Hj-receptors participate in the regulation of blood pressure, body temperature, fluid homeostasis, and pain sensation. Presynaptic Hj-receptors serve as feedback inhibitors of the release of histamine, norepinephrine, and other neurotransmitters. 

In the periphery, Hi-receptors on sensory neurons in the epidermis and dermis mediate itch and pain, respectively. Autonomic afferent nerve endings may be similarly stimulated by histamine. As in the CNS, presynaptic Hj-receptors act in a feedback inhibitory capacity. 

Nerve endings 5-HT is less potent than histamine in releasing catecholamines from adrenal medulla. S-HT receptors located on various sensory neurons mediate a depolarising response, which may cause pain itching. 

Inflammation A protective tissue response to injury that serves to destroy, dilute, or wall off both the injurious agent and the injured tissue. It is characterized by symptoms such as pain, heat, and redness and is the result of the combined effects of numerous inflammatory mediators (e.g., prostaglandins, histamine, cytokines, etc.). 

Allergic responses to drugs are mediated by the release of histamine or histamine-like substances, and they commonly present as skin rashes, particularly urticaria. More serious hypersensitivity responses include bronchospasm or the acute, explosive anaphylactic reaction with cyanosis and cardiovascular collapse. A delayed reaction known as serum sickness, although more often associated with such drugs as the penicillins and cephalosporins rather than with serum, manifests clinically 7 to 10 days after receiving the drug or serum as fever, malaise, joint pains, and urticarial skin rashes. 

Histamine released from mast cells plays an important physiological role in immediate hypersensitivity and allergic responses. In addition, histamine functions as a neurotransmitter in the CNS and it is a potent stimulus for gastric acid secretion. These actions depend on the interaction of histamine with two types of receptors, Hi and H2. Hi and H2 receptors are coupled via G proteins to phospholipase C and adenylyl cyclase, respectively. The principal H3 receptor response is stimulation of gastric acid secretion, whereas other actions of histamine (e.g., smooth muscle contraction, vasodilation, increased capillary permeability, pain, and itching) are prunarily mediated by Hi receptors. 

Moderate doses (2 tablets) inhibit formation of PGs, which sensitize peripheral pain receptors to algesic mediators such as bradykinin and histamine. 

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