Peripheral Sensitization

Abstract

Peripheral sensitization indicates increased responsiveness and reduced threshold of nociceptive neurons in the periphery to the stimulation, which usually occurs after peripheral tissue injury and inflammation. As an integral part of pain, peripheral sensitization and its mechanisms have received much attention, and numerous types of neurotransmitters and chemicals related to peripheral sensitization were investigated. We developed an animal model of peripheral sensitization, and it provides evidence that some neurotransmitters, such as glutamate and substance P, release from adjacent peripheral nerves contributing to the peripheral sensitization of pathological pain. In this chapter, we reviewed the advances in peripheral sensitization, and it will provide a basis for new targets to attenuate pain of peripheral origin.Several animal models of various pain states have been established to investigate the mechanisms of peripheral sensitization, for example, inflammation pain models, neuropathic pain evoked by disease or damage to peripheral nerves, and post-operative pain models. Animal models of inflammatory pain have used a number of different irritants that are injected into skin, paw, muscle, joint, and visceral organ. Carrageenan, complete Freund's adjuvant (CFA), and capsaicin are commonly used inflammatory irritants to induce hyperalgesia. Common nerve injury models include: (1) ligating or transecting the spinal nerves, such as spinal nerve ligation model (SNL); (2) ligating or lesioning the sciatic nerve, such as chronic constriction injury (CCI); and (3) ligating distal branches (peroneal and tibial) of the sciatic nerve (spared nerve injury) [16].To better understand the mechanisms of transmission between peripheral sensory nerve endings, we have successfully established an electrophysiological animal model in which antidromic electrical stimulation of a sensory nerve excites the adjacent primary afferents from the different spinal segments [17]. In this model, two adjacent cutaneous branches of spinal dorsal rami in the thoracic segments, T9 and T10, were dissociated and transected proximally from the spinal cord in anesthetized rats. Then antidromic electrical stimulation with 0.5 ms pulse duration, 20 Hz frequency, and 1 mA intensity was applied to T9 spinal nerve branch, and the nerve activities of T10 nerve branch were recorded [18]. All recorded afferent neurons from the T10 cutaneous branch were classified as Aβ, Aδ, and C fibers according to the conduction velocity and the receptive properties [19]. The discharges of the isolated Aβ, Aδ, and C fibers of the T10 cutaneous branch were significantly enhanced by antidromic electrical stimulation of the adjacent T9 spinal nerve branch [18]. It is in line with our previous studies that antidromic stimulation of T9 spinal nerve branch can activate and sensitize Aβ, Aδ, and C fibers obtained from the adjacent T10 dorsal cutaneous branch [20][21][22][23]. The activation and sensitization of these fibers not only occur between the peripheral sensory nerve...

Cervical Spondylosis as a Hidden Contributing Factor to Fibromyalgia: A Case Report

“…20 This process is known as peripheral sensitization, which is a reduction in spike threshold and amplification in the responsiveness of peripheral sensory nerve fibers for an external stimulation. 13,21 Structural abnormalities of C-fibers and altered C-fiber efferent function might play a role in FM. 18 There may be multiple subsets of FM with different etiopathogenesis.…”

Peripheral Sensitization

“…In addition, glutamate-induced excitatory response was significantly enhanced by coinjection of subthreshold doses of SP [142]. Effects of glutamate and SP on spinal dorsal horn neurons may result from co-release of these two mediators from the same dorsal root afferent terminals [143].…”

“…The activation of TRPV1 increases the calcium permeability of the receptor, priming membrane depolarization and subsequent sensory neuron activation [44,51]. The TRPV1 receptor occupancy triggers Na + and Ca 2+ influx, action potential firing, and the consequent burning sensation associated with spicy food or capsaicin-induced pain [44].…”

Peripheral Mechanisms of Neuropathic Pain—The Role of Neuronal and Non-Neuronal Interactions and Their Implications for Topical Treatment of Neuropathic Pain

“… peripheral sensitization-hyperexcitability of sensory neurons due to lowered threshold and augmented response to suprathreshold stimuli, caused by peripheral nerve or tissue injury, inflammation and subsequent release of pro-nociceptive mediators from mast cells, macrophages and from neighbouring nerve terminals, such as prostaglandins, bradykinin, histamine, serotonin, SP (substance P), extracellular ATP (adenosine triphosphate), protons, cytokines, chemokines, growth factors, peptides, acting on corresponding receptors, ion channels or altering their sensitivity to stimuli [8,29,30];…”

“…The molecular processes involved in neuroinflammation and peripheral sensitization are presented on Figure 1 [8,22,[29][30][31][32][33][34][35][36][37][38][39][40]. VGCC-voltage-gated calcium channel, Glu-glutamate, H + -hydrogen proton, NMDAR-N-methyl-D-aspartate receptor, ASIC-acid sensing ion channel, TLR-toll-like receptor, P2X3-P2X purinoceptor 3, PGE2-prostaglandin E2, EP-prostaglandin E2 receptor, GABA-gamma-aminobutyric acid, GABAAR-gamma-aminobutyric acid receptor A, GABABR-gamma-aminobutyric acid receptor B, Kv-voltage-gated potassium channel, OR-opioid receptor, CB-cannabinoid, CB1-cannabinoid receptor type 1, HMBG1-high mobility group box 1 protein, TNFα-tumour necrosis factor α, IL-1β-interleukin 1β, IL-6-interleukin 6, CCL-CC-chemokine ligand, ATP-adenosine triphosphate, NGF-nerve growth factor, BDNF-brain-derived neurotrophic factor, GDNF-glial-derived neurotrophic factor, NT 3,4-neurotrophin 3 and 4, Na + -sodium ion, Ca 2+ -calcium ion, K + -potassium ion, BK-bradykinin, 5-HT-serotonin, GPCR-G protein-coupled receptor.…”