Comparison of the peripheral mediator background of heat injury- and plantar incision-induced drop of the noxious heat threshold in the rat

Füredi, Réka; Bölcskei, Kata; Szolcsányi, Janós; Pethő, Gábor

doi:10.1016/j.lfs.2009.12.010

Cited by 14 publications

(9 citation statements)

References 49 publications

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“…Interleukins (IL-1β, IL-6 and IL-10) were upregulated in skin and muscle after incision [50], while IL-6 can enhance the activity of the TRPV1 receptor [56]. Also, the activation of peripheral bradykinin receptors (B1, B2), P2X purinoceptors, cyclooxygenase (COX) and nitric oxide (NO) synthase [13,57] was shown to have a role in incisional thermal hyperalgesia. Bradykinin, prostaglandins and ATP were found to sensitize the TRPV1 receptor to heat [58][59][60], while NO was shown to activate the TRPV1 receptor via S-nitrosylation of cysteine residues [61].…”

Section: Discussionmentioning

confidence: 99%

“…Sensitization of a broad spectrum of sensory nerve fibers (C, Aδ and Aβ) occurs after incision at the peripheral and/or spinal cord level [ 4 , 7 ]. In the peripheral tissues, neutrophils [ 8 ], acidosis [ 9 ], nerve growth factor (NGF) [ 10 , 11 ], EP 1 receptor [ 12 ], B 1 and B 2 bradykinin receptors, P2X purinoceptors, transient receptor potential vanilloid 1 (TRPV1) receptor, nitric oxide (NO) synthase, lipoxygenase [ 13 ], insulin-like growth factor 1 (IGF-1) [ 14 ], acid-sensing ion channel 3 [ 15 ], the activation of AMP-activated protein kinase that inhibits IL-6 mediated signaling to ERK [ 16 ] and others could contribute to postoperative pain. In the spinal cord cyclooxygenase (COX) [ 17 , 18 ], the EP 1 receptor for a product of COX metabolism - prostaglandin E 2 [ 19 ], brain derived neurotrophic factor (BDNF) [ 20 ], glial cell activation and interleukin-1 beta (IL-1β) [ 21 ], the chemokine CCL2 [ 22 ], serotonin receptors [ 23 ], GABA A and GABA B receptors [ 24 ], calcium/calmodulin-dependent protein kinase IIα [ 5 ], p38 mitogen-activated protein kinase (p38 MAPK) [ 25 ], phosphatidylinositol 3-kinase (PI3K) [ 26 ] and others could contribute to the hypersensitivity induced by plantar incision.…”

Section: Introductionmentioning

confidence: 99%

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TRPV1 Antagonist Attenuates Postoperative Hypersensitivity by Central and Peripheral Mechanisms

2014

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BackgroundAcute postoperative pain is one of the frequent reasons for pain treatment. However, the exact mechanisms of its development are still not completely clear. Transient receptor potential vanilloid 1 (TRPV1) receptors are involved in nociceptive signaling in various hypersensitive states. Here we have investigated the contribution of TRPV1 receptors expressed on cutaneous peripheral nociceptive fibers and in the spinal cord on the development and maintenance of hypersensitivity to thermal and mechanical stimuli following surgical incision. A rat plantar incision model was used to test paw withdrawal responses to thermal and mechanical stimuli. The effect of the TRPV1 receptor antagonist SB366791 was investigated 1) by intrathecal injection 15 min before incision and 2) intradermal injection before (30 min) and immediately after the surgery. Vehicle-injected rats and naïve animals treated identically were used as controls.ResultsPlantar incision induced mechanical allodynia and hyperalgesia and thermal hyperalgesia. A single intrathecal administration of SB366791 significantly reduced postincisional thermal hyperalgesia and also attenuated mechanical allodynia, while mechanical hyperalgesia remained unaffected. Local intradermal SB366791 treatment reduced thermal hyperalgesia and mechanical allodynia without affecting mechanical hyperalgesia.ConclusionsOur experiments suggest that both peripheral and spinal cord TRPV1 receptors are involved in increased cutaneous sensitivity following surgical incision. The analgesic effect of the TRPV1 receptor antagonist was especially evident in the reduction of thermal hyperalgesia. The activation of TRPV1 receptors represents an important mechanism in the development of postoperative hypersensitivity.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

TRPV1 Antagonist Attenuates Postoperative Hypersensitivity by Central and Peripheral Mechanisms

2014

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“…Skin P2X3R expression was increased on sensory nerve terminals in first and second degree burns, but, following treatment with tetramethylpyrazine, P2X3R expression was reduced. P2X3R may play a role in the short-lasting thermal hyperalgesia induced by mild heat injury ( Füredi et al, 2010 ). After a superficial skin burn, adenosine reduced the skin area showing hypersensitivity.…”

Section: Skin Diseasesmentioning

confidence: 99%

Purinergic Signalling: Therapeutic Developments

2017

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Purinergic signalling, i.e., the role of nucleotides as extracellular signalling molecules, was proposed in 1972. However, this concept was not well accepted until the early 1990’s when receptor subtypes for purines and pyrimidines were cloned and characterised, which includes four subtypes of the P1 (adenosine) receptor, seven subtypes of P2X ion channel receptors and 8 subtypes of the P2Y G protein-coupled receptor. Early studies were largely concerned with the physiology, pharmacology and biochemistry of purinergic signalling. More recently, the focus has been on the pathophysiology and therapeutic potential. There was early recognition of the use of P1 receptor agonists for the treatment of supraventricular tachycardia and A2A receptor antagonists are promising for the treatment of Parkinson’s disease. Clopidogrel, a P2Y12 antagonist, is widely used for the treatment of thrombosis and stroke, blocking P2Y12 receptor-mediated platelet aggregation. Diquafosol, a long acting P2Y2 receptor agonist, is being used for the treatment of dry eye. P2X3 receptor antagonists have been developed that are orally bioavailable and stable in vivo and are currently in clinical trials for the treatment of chronic cough, bladder incontinence, visceral pain and hypertension. Antagonists to P2X7 receptors are being investigated for the treatment of inflammatory disorders, including neurodegenerative diseases. Other investigations are in progress for the use of purinergic agents for the treatment of osteoporosis, myocardial infarction, irritable bowel syndrome, epilepsy, atherosclerosis, depression, autism, diabetes, and cancer.

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“…As an example, mechanical hyperalgesia is effectively reduced by gabapentinoids, while inhibition of P2X purinoceptors has been shown to ameliorate thermal hyperalgesia. 36,37 Furthermore, the ongoing spontaneous activity observed in sensory neurons after incision is responsible for nonevoked pain (pain at rest). This suggests that analgesics targeting nociceptors (ie, transient receptor potential cation channel subfamily V member 1 [TRPV1]) responsible for the increased spontaneous firing in small sensory neurons can effectively blockade pain at rest.…”

Section: Acute and Persistent Postoperative Pain: Mechanismsmentioning

confidence: 99%

Role of Micro-RNA for Pain After Surgery: Narrative Review of Animal and Human Studies

Cata

Görür

Yuan

et al. 2020

Anesthesia &Amp; Analgesia

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One of the most prevalent symptoms after major surgery is pain. When postoperative pain treatment is unsatisfactory, it can lead to poor surgical recovery, decreased quality of life, and increased health care costs. Current analgesics, single or in combination, have limited efficacy due to low potency, limited duration of action, toxicities, and risk of addiction. The lack of nonaddictive strong analgesics along with the over prescription of opioids has led to an opioid epidemic in the United States. Therefore, there is an urgent need for the development of newer analgesics. Microribonucleic acids (miRNAs) are small noncoding RNA molecules that modulate protein synthesis in neurons and supporting cells (glia, leukocytes, and Schwann cells). The literature indicates that miRNA regulation is important in nociception. Here, we summarize the current evidence on the role of miRNAs on mechanisms involved in incisional, inflammatory, neuropathic, and cancer pain. We also discuss the role of modulating miRNA functions as potential therapeutic targets for analgesic use and opioid tolerance. Finally, we propose how the

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Comparison of the peripheral mediator background of heat injury- and plantar incision-induced drop of the noxious heat threshold in the rat

Cited by 14 publications

References 49 publications

TRPV1 Antagonist Attenuates Postoperative Hypersensitivity by Central and Peripheral Mechanisms

TRPV1 Antagonist Attenuates Postoperative Hypersensitivity by Central and Peripheral Mechanisms

Purinergic Signalling: Therapeutic Developments

Role of Micro-RNA for Pain After Surgery: Narrative Review of Animal and Human Studies

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