Thermal nociceptors

Nociceptors Receptors for pain caused by injury from physical stimuli (mechanical, electrical, or thermal) or chemical stimuli (toxins). Nociceptors are located in the skin, muscles, and in the walls of the viscera. 

Thermal nociceptors and mechanical nociceptors are associated with A-delta fibers. These are small myelinated fibers that transmit impulses at a rate of 5 to 30 m/sec. Polymodal nociceptors are associated with C fibers. These are small unmyelinated fibers that transmit impulses at a rate generally less than 1.0 m/sec (range of 0.5 to 2.0 m/sec). 

Primary sensory neurons sense pain and convey it to the spinal cord. Nociceptors have unmyelinated (C fiber) or thinly myelinated (AS) axons, while the low-threshold Ap-fiber mechanoreceptors involved in tactile and proprioceptive perception have large myelinated sensory neurons (Table 57-1). The peripheral terminals of primary sensory neurons convert changes in the environment into neuronal activity by transducing mechanical (Ch. 51), thermal or chemical stimuli into ion fluxes across their... 

FIGURE 57-2 Noxious chemical, thermal and mechanical stimuli activate specific high-threshold receptors and ion channels that lead to inward currents in the peripheral terminals of nociceptors. 

Stimulation of free nerve endings known as nociceptors is the first step leading to the sensation of pain. These receptors are found in both somatic and visceral structures and are activated by mechanical, thermal, and chemical factors. Release of bradykinins, K1, prostaglandins, histamine, leukotrienes, serotonin, and substance P may sensitize and/or activate nociceptors. Receptor activation leads to action potentials that are transmitted along afferent nerve fibers to the spinal cord. 

Activation of nociceptor PKRs by Bv8 in rats and mice produces nociceptive sensitization to thermal and mechanical stimuli, without inducing any spontaneous, overt nocifensive behavior, or local inflammation. Very low doses of Bv8 (50 fmol) injected into the paw induce a decrease in the nociceptive threshold that reaches the maximum in 1 h and disappears in 2-3 h. The same dose i.th., or higher doses by systemic routes (s.c. and i.v.), induces hyperalgesia with a characteristic biphasic time-course the first peak occurs in 1 h and the second peak invariably in 4—5 h. The first phase depends on a direct action on nociceptors, because it resembles that... 

Malin SA, Molliver DC, Koerber HR, Comuet P, Frye R, Albers KM, Davis BM (2(X)6) Glial cell hne-deiived neurotrophic factor family members sensitize nociceptors in vitro and produce thermal hyperalgesia in vivo. J Neurosci 26 8588-8599 Malkmus S, Lu X, Bartfai T, Yaksh TL, Hua XY (2005) Increased hyperalgesia after tissue injury and faster recovery of allodynia after nerve injury in the GalRl knockout mice. Neuropeptides 39 217-221... 

Sensory nerve endings are found throughout the body in the skin, muscles, joints, blood vessels and internal organs. These nociceptors are sensitive to the effects of potentially damaging mechanical, thermal and chemical stimuli. 

Natural products are fundamental to pain treatment. They yield new analgesics and play an important role in the study of pain mechanisms [for review see 1,2]. Pain is defined as an unpleasant sensory and emotional experience associated with actual or potential tissue damage. Alternatively, it can be described in terms of such damage [3]. The sensory component of pain (nociception) is triggered by mechanical, thermal, or chemical noxious stimuli at the free ends of small diameter primary afferent fibres (nociceptors) present in practically all body tissues [4,5]. After tissue damage, several mediators, such as bradykinin,... 

Rueff A, Mendell L M (1996). Nerve Growth Factor and NT-5 induce increased thermal sensitivity of cutaneous nociceptors in vitro. /. Neurophysiol. 76 3596-3596. 

Whenever mechanical, thermal, or chemical stimulation of the skin is increased beyond a specific level, pain is felt along with the stimulus-induced perception nociceptors transmit this type of sensation. The warning signal called pain is generally perceived in two different ways ... 

Nociceptors convey noxious sensation, either externally (i.e. skin, mucosa) or internally (i.e. joints, intestines). They can be activated by any noxious insult, most of which can be categorized as either mechanical, chemical, or thermal in nature. Nociceptor activation is associated with a depolarizing Ca + current or a generator potential . Once a certain threshold is met, the distal axonal segment depolarizes via an inward Na+ current, and an action potential is conducted centrally. 

Capsaican is a TRPV-1 agonist. TRPVl (also termed the capsaican receptor) is a polymodal nociceptor exhibiting a dynamic threshold of activation that is markedly reduced in inflammatory conditions [3]. TRPVl knock-out mice are devoid of post-inflammatory thermal hyperalgesia. TRPV receptors are in abundance on unmyelinated C fiber peripheral endings and respond to a variety of noxious mediators. Once activated these fibers transmit localized and... 

Of these receptor sites, it is the distinct subsets of thermoreceptors in combination with nociceptors that give the sensations of heat and cooling by chemical stimulus in the mouth. In mammals it is proposed that a set of ion channels, called transient receptor potential (TRP) channels, are the primary molecular transducers of thermal stimuli. One such molecular transducer is the vanilliod receptor (VRl) channel, which is an ion-gated channel that is activated by temperatures above 43°C and by chemical irritants, such as, capsaicin and acidic pH [34]. Vanilliod receptor. 

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