Nociceptive Pain

Nociceptors are cutaneous and subcutaneous receptors specialized for the detection of noxious stimuli (Latremoliere & Woolf, 2009). Nociception is considered a protective process designed to help prevent injury by producing a withdrawal reflex from the stimulus and by generating an unpleasant sensation resulting in behavioral strategies to avoid further contact with the stimuli (Latremoliere & Woolf, 2009). Pain can be divided into nociceptive pain or neuropathic pain since each type of pain has a different mechanism. Nociceptive pain results from direct activation of pain nerve fibers from inflammatory, mechanical or chemical mediators, whereas neuropathic pain generally refers to pain that is initiated or sustained by a primary lesion or

Prostaglandins contribute to peripheral sensitization by binding to G-protein coupled receptors that increase the levels of cyclic AMP within nociceptors. Prostaglandins also reduce the threshold depolarization required for generating action potentials by phosphorylating a specific class of TTX-resistant sodium channels, TTX-R Na+, that are expressed only in nociceptors (Kidd & Urban, 2001). In addition, some nociceptors can be sensitized by the MAPK mediated pathway. MAPKs are normally inactive in neurons, but they become activated when they are phosphorylated by other kinases. The MAPK family contains three separate signaling pathways: extracellular signal-regulated kinases (ERK), p38 and c-Jun N-terminal kinase (Ji, et al., 2009). All three of these MAPK pathways contribute to pain sensitization after tissue and nerve injury by distinct molecular and cellular mechanisms. ERK is one of the best-characterized pathways of the MAPK family (Ji, et al., 2009). During noxious conditions and inflammation, there is an increase in peripheral levels of ATP, bradykinin, neurotrophins, protons, ATP and other mediators resulting in sensitization of peripheral sensory fibers and an increased amount of neurotrophins and glutamate in the cytoplasm of spinal neurons (Cruz & Cruz, 2007). When the neurotrophins and glutamate bind to their respective receptors, the ERK

Neuropathic pain is a frequent complication of pathological conditions such as AIDS, stroke, diabetes, multiple sclerosis and shingles (Campbell & Meyer, 2006). Neuropathic pain can arise spontaneously or by mild stimuli that are common to everyday experience like gentle touch, warm and cool temperatures, and pressure of clothing (Campbell & Meyer, 2006). Patients often describe their experience as lancinating or continuous burning pain. Much present research is being devoted to better understand the mechanisms of neuropathic pain due to its debilitating effect. Both central and peripheral pain related factors have been associated with neuropathic pain, and it is possible that any one of these factors, or a combination, contribute to the symptomatology of patients experiencing neuropathic pain (Campbell & Meyer, 2006). Peripheral effects include ectopic and spontaneous discharge, alterations in ion channel expression, collateral sprouting of primary afferent neurons, sprouting of sympathetic neurons into the dorsal root ganglion, and nociceptor sensitization (Campbell & Meyer, 2006). Central effects include central sensitization, spinal reorganization, cortical reorganization, and changes in inhibitory pathways (Campbell & Meyer, 2006). In addition, the mechanism of nociceptor sensitization in neuropathic pain can be divided into the