Nociceptive nerve fibers

The decreased work capacity of the in-farcted myocardium leads to a reduction in stroke volume (SV) and hence cardiac output (CO). The fall in blood pressure (RR) triggers reflex activation of the sympathetic system. The resultant stimulation of cardiac 3-adreno-ceptors elicits an increase in both heart rate and force of systolic contraction, which, in conjunction with an a-adren-oceptor-mediated increase in peripheral resistance, leads to a compensatory rise in blood pressure. In ATP-depleted cells in the infarct border zone, resting membrane potential declines with a concomitant increase in excitability that may be further exacerbated by activation of p-adrenoceptors. Together, both processes promote the risk of fatal ventricular arrhythmias. As a consequence of local ischemia, extracellular concentrations of H+ and K+ rise in the affected region, leading to excitation of nociceptive nerve fibers. The resultant sensation of pain, typically experienced by the patient as annihilating, reinforces sympathetic activation. 

Topical products can be used alone or in combination with oral analgesics or NSAIDs. Capsaicin, isolated from hot peppers, releases and ultimately depletes substance P from afferent nociceptive nerve fibers. Substance P has been implicated in the transmission of pain in arthritis, and capsaicin cream has been shown in four controlled studies to provide pain relief in OA when applied over affected joints. " ... 

Fig. 4.1 Hypothetical model of pathogenesis of pain in DSP. (1) Injury of peripheral nerve fibers due to multifocal inflammation and secreted macrophage activation products results in abnormal spontaneous activity of neighboring uninjured nociceptive fibers ( peripheral sensitization ). (2) Furthermore, the aberrant inflammatory response in DRG leads to alterations in neuronal sodium and calcium channel expression and ectopic impulse generation. (3) This results in central remodeling within the dorsal horn due to A-fiber sprouting and synaptic formation with pain fibers in lamina 11, and maintenance of neuropathic pain ( central sensitization ). Reproduced with permission from (Keswani et al. 2002)...

Fleetwood-Walker, S. M., Mitchell, R., Hope, P. J., El-Yassir, N., Molony, V. The roles of tachykinin and opioid receptor types in nociceptive and non-nociceptive processing in superficial dorsal horn. In Fine afferent nerve fibers and pain, 1987, edited by R. F. Schmidt, H. G. Schaible, C. Vahle-Hinz, 239-247, VCH, Weinheim. 

Nociceptive transmission takes place in A5 and C-afferent nerve fibers. Stimulation of large-diameter, sparsely myelinated A5 fibers evokes sharp, well-localized pain, whereas stimulation of unmyelinated, small-diameter C fibers produces dull, aching, and poorly localized pain. These afferent, nociceptive pain fibers synapse in various layers (laminae) of the spinal cord s dorsal hom, releasing a... 

Cetirizine competitively antagonizes histamine at the Hi-receptor site and is indicated in the symptomatic relief of symptoms (e.g., nasal, nonnasal) associated with seasonal and perennial allergic rhinitis treatment of uncomplicated skin manifestations of chronic idiopathic urticaria. Histamine is a potent vasodilator, bronchial smooth-muscle constrictor, and stimnlant of nociceptive itch nerves. In addition to histamine, mnltiple chemical itch mediators can act as pruritogens on C-fibers, including neuropeptides, prostaglandins, serotonin, acetylcholine, and bradykinin. Furthermore, new receptor systems such as vanilloid, opioid, and canna-binoid receptors on cutaneous sensory nerve fibers that may modulate itch offer novel targets for antipruritic therapy. 

High sensitivity of sensory nerves, low sensitivity of motor nerves. Impulse conduction in sensory nerves is inhibited at a concentration lower than that needed for motor fibers. This difference may be due to the higher impulse frequency and longer action potential duration in nociceptive, as opposed to motor, fibers. 

High sensitivity of sensory, low sensitivity of motor nerves. Impulse conduction in sensory nerves is inhibited at a concentration lower than that needed for motor fibers. This difference may be due to the higher impulse frequency and longer action potential duration in nociceptive as opposed to motor fibers. Alternatively, it may relate to the thickness of sensory and motor nerves, as well as the distance between nodes of Ranvier. In saltatory impulse conduction, only the nodal membrane is depolarized. Because depolarization can still occur after blockade of three or four nodal rings, the area exposed to a drug concentration suf cient to cause blockade must be larger for motor fibers (p. 203B). 

Local anesthetics are used in the clinical situation to interrupt the nociceptive process at one or more points between the peripheral, high-threshold nociceptor and the cerebral cortex, by blocking transduction by infiltration at the site of injury or incision by preventing transmission in afferent myelinated A 8 and unmyelinated C fibers by blockade of peripheral nerves or nerve plexuses or by epidural injection. 

Histamine is a potent vasodilator, bronchial smooth muscle constrictor, and stimulant of nociceptive itch nerves. In addition to histamine, multiple chemical itch mediators can act as pruritogens on C-fibers, including neuropeptides, prostaglandins, serotonin, acetylcholine, and bradykinin. 

Substance P is a neuropeptide released from the unmyelinated primary afferent fibers, and its role in nociception is well established. Its effects can be blocked by treatment with the neurotoxin capsaicin, which destroys afferent nerve terminals. The pro-inflammatory effects of substance P include vasodilatation and plasma extravasation, degranulation of mast cells, resulting in histamine release, chemo-attraction and proliferation of leukocytes, and cytokine release. 

Neuropathic pain is distinct from normal, nociceptive pain triggered by noxious stimuli. It is believed to be triggered by persistent nociceptive stimuli or frank nerve injury. These conditions activate a series of adaptive and, eventually, maladaptive changes in the function and properties of pain-carrying fibers and other sensory neurons, including phenotypic changes and alterations in gene expression, as well as the fundamental properties of specific neurons and sensory... 

D. Brenn, F. Richter, H. Schaible, Sensitization of unmyelinated sensory fibers o the joint nerve to mechanical stimuli by interleukin-6 in the rat An inflammator mechanism of joint pain. Arthritis Rheum., 56 (1), 351-359,2007. http //dx.doi.org/10.1002/art.22282. K.J. Bar, et al. Changes in the effect of spinal prostaglandin E2 during inflammation Prostaglandin E (EP1-EP4) receptors in spinal nociceptive processing of input from the normal or inflamed knee joint, J. Neuroscl, 24 (3), 642-651, 2004. http //dx.doi.org/ 10.1523/JNEUROSCI.0882-03.2004. 

---