Nociceptors activation

Neuropathic pain states are thought to be generated in the peripheral sensory neurons by events within the nerve itself and so are independent of peripheral nociceptor activation. Damage to peripheral nerves can be caused by a number of pathological, metabolic and viral causes. According to the terminology guide of the International... 

Inflammatory pain results from changes both in primary sensory and dorsal horn neurons 933 Peripheral sensitization lowers nociceptor activation threshold 933... 

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. 

Primary hyperalgesia follows primary nociceptor activation (or transduction) in response to mechanical. 

Clearly nociceptor activity plays a role in post-surgical pain. The most effective treatment of classic nociceptor pathways is mu-agonist opioids. There are many to select from and the decision is largely based on the severity of post operative pain and the anticipated dmation of nociceptive firing. 

Antiepileptics are used in neuropathic pain resulting from lesions to the peripheral (e.g., diabetes, heipes) or central nervous system (e.g., stroke). Such syndromes have been attributed to ectopic activity in sensitized nociceptors from regenerating nerve sprouts, recruitment of previously silent nociceptors, and/or spontaneous neuronal activity. This may result in sensitization... 

Bradykinin is also released from mast cells within damaged tissues. It produces inflammation and activates nociceptors via bradykinin B1 and B2 receptors. 

Nociceptors are a specific subset of peripheral sensory organs, which respond to noxious stimuli. A8 mechan-oreceptors and C-polymodal nociceptors are the two main classes of cutaneous nociceptors. The sensory quality of pain evoked by activation of A8-fibres is... 

Hydrogen ions accumulate in tissue damaged by inflammation and ischaemia and so pH is lowered. These protons may activate nociceptors directly via their own family of ion channels as well as sensitising them to mechanical stimulation. Acid-sensing ion channels (ASICS) are a family of sodium channels that are activated by protons — of special interest is one type found only in small dorsal root ganglion neurons that possibly are responsible for activation of nociceptors. Although the transduction of mechanical stimuli is poorly understood, ASICs are closely related to channels that respond to stretch. 

Nerve receptors, or nociceptors, may release substance P, a peptide that causes vasodilation when released.20 This dilation occurs mainly through substance P-induced production of the vasodilator nitric oxide. Substance P also generates the release of histamine, leading to bradykinin release and activation of an inflammatory process. Capsaicin relieves pain by stimulating the release of substance P from sensory nerve fibers, which ultimately depletes stores of substance P. 

Describe the three types of nociceptors and the stimuli that activate them... 

Table 8.1 Endogenous Chemicals Activating or Sensitizing Nociceptors... 

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... 

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