Pain mediator

Growth hormone, corticotropin, thyrotropin, luteinizing hormone, thyroid hormone, insulin, glucocorticoids, progesterone, erythropoietin, renin Increased body temperature Sensitization of pain-mediating nerve fibers Increased force of myocardial contraction... 

Skeletal muscle spasms are used to describe the increased tension often seen in skeletal muscle after certain musculoskeletal injuries and inflammation (muscle strains, nerve root impingements, etc.) occur.20,96 This tension is involuntary, so the patient is unable to relax the muscle. Spasms differ from spasticity because spasms typically arise from an orthopedic injury to a musculoskeletal structure or peripheral nerve root rather than an injury to the CNS. Likewise, muscle spasms are often a continuous, tonic contraction of specific muscles rather than the velocity-dependent increase in stretch reflex activity commonly associated with spasticity. The exact reasons for muscle spasms are poorly understood. According to some authorities, muscle spasms occur because a vicious cycle is created when the initial injury causes muscular pain and spasm, which increases afferent nociceptive input to the spinal cord, further exciting the alpha motor neuron to cause more spasms, and so on.61,96 Other experts believe that muscle spasms occur because of a complex protective mechanism, whereby muscular contractions are intended to support an injured vertebral structure or peripheral joint.96 Regardless of the exact reason, tonic contraction of the affected muscle is often quite painful because of the buildup of pain-mediating metabolites (e.g., lactate). 

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... 

FIGURE 14-2 Schematic representation of how opioid analgesics may impair synaptic transmission in pain-mediating pathways. The drug binds to specific opioid receptors on the presynaptic and postsynaptic membranes. 

Rubefacients are compounds that produce local vasodilation and create a sensation of warmth, exerting an analgesic effect by masking the perception of pain. Massaging enhances their effect and also helps to disperse local tissue pain mediators. 

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

The term indirect response refers to a PD response that is produced by a drug s action on the production or dissipation of endogenous factors that affect the response. Thus, the measured response is indirectly related to the direct effect produced by the drug at the site of action for example, the reduction in pain by the inhibitory action of nonsteroidal anti-inflammatory drugs on the production of endogenous pain mediators. 

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),... 

These, in turn, reduce membrane excitability through a number of possible mechanisms, including changes in membrane fluidity, permeability, and receptor/channel functions. Furthermore, local anesthetics, in contrast to analgesic compounds, do not interact with the pain receptors or inhibit the release or the biosynthesis of pain mediators. 

Field MJ, Cox PJ, Stott E, Melrose H, Offord J, Su TZ, BramweU S, et al. Identification of the alpha2-delta-1 subunit of voltage-dependent calcium channels as a molecular target for pain mediating the analgesic actions of pregabahn. Proc Natl Acad Sci USA 2006 103(46) 17537-42. 

Jamali, F. Kunz-Dober, C.M. Pain-mediated altered absorption and metabolism of ibuprofen an explanation for decreased serum enantiomer concentration after dental surgery. Br. J. Clin. Pharmacol. 1999, 47, 391-396. 

It is common to all receptors that, in case of binding to agonistic opioids, they reduce the neurotransmitter concentration in the synaptic gap of the pain-mediating nerve tract. 

A general anti-inflammatory action may be very important for pain reduction per se, by reducing local tissue pressure and limiting the release of potent pain mediators. The glucocorticoids have also been shown to have direct effects on pain neurons and receptors. 

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