Transient Receptor Potential Vanilloid 1 Mediates Hyperalgesia and Is Up-Regulated in Rats With Chronic Pancreatitis

Xu, Guang–Yin; Winston, John H.; Shenoy, Mohan; Yin, Huaizhi; Pendyala, Swaroop; Pasricha, Pankaj J.

doi:10.1053/j.gastro.2007.06.015

Cited by 120 publications

(105 citation statements)

References 47 publications

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“…Intrathecal pretreatment with SB366791, a selective TRPV1 antagonist (Gunthorpe et al, 2004;Lappin et al, 2006;Xu et al, 2007), reduced morphine tolerance and associated thermal hyperalgesia without affecting the basal pain threshold of the control animals, suggesting that this receptor is involved in the effects induced by chronic morphine. Interestingly, acute morphine treatment inhibited, via a cAMP/PKA-dependent pathway, capsaicin-induced TRPV1 activity and thermal hyperalgesia (Endres-Becker et al, 2007).…”

Section: Discussionmentioning

confidence: 99%

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Activation of TRPV1 Contributes to Morphine Tolerance: Involvement of the Mitogen-Activated Protein Kinase Signaling Pathway

Chen¹,

Geis²,

Sommer³

2008

J. Neurosci.

142

141

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Tolerance to the analgesic effects of opioids occurs after their chronic administration, a pharmacological phenomenon that has been associated with the development of abnormal pain sensitivity such as hyperalgesia. In the present study, we investigated the role of TRPV1, which is crucial for the transduction of noxious chemical and thermal stimuli, in morphine tolerance and tolerance-associated thermal hyperalgesia. After chronic morphine treatment, a marked increase in TRPV1 immunoreactivity ( Chronic morphine exposure induced increases in phosphorylation of mitogen-activated protein kinases (MAPKs), including p38 MAPK-IR, extracellular signal-regulated protein kinase (ERK)-IR, and c-Jun N-terminal kinase (JNK)-IR, in L4 DRG neurons.Intrathecal administration of the selective p38, ERK, or JNK inhibitors not only reduced morphine tolerance and associated thermal hyperalgesia but also suppressed the morphine-induced increase of TRPV1-IR in DRG neurons, spinal cord, and sciatic nerve and of mRNA levels in spinal cord and sciatic nerve. Together, we have identified a novel mechanism by which sustained morphine treatment results in tolerance and tolerance-associated thermal hyperalgesia, by regulating TRPV1 expression, in a MAPK-dependent manner. Thus, blocking TRPV1 might be a way to reduce morphine tolerance.

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Section: Discussionmentioning

confidence: 99%

“…Once daily intrathecal injection of SB366791, a selective TRPV1 antagonist (Gunthorpe et al, 2004;Lappin et al, 2006;Xu et al, 2007), produced no effect on the basal thermal pain thresholds in rats receiving NS throughout the whole observation period (Fig. 5, SB366791 ϩ NS group).…”

Section: Blockade Of Trpv1 Attenuates Morphine Tolerance and Associatmentioning

confidence: 97%

Activation of TRPV1 Contributes to Morphine Tolerance: Involvement of the Mitogen-Activated Protein Kinase Signaling Pathway

Chen¹,

Geis²,

Sommer³

2008

J. Neurosci.

142

141

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“…Enhanced activity in potassium channels and transient receptor potential vanilloid 1 (TRPV1) has been demonstrated in a rat model of chronic pancreatitis. 26,27 Nerve growth factor, important in nociceptive sensitization, has increased pancreatic expression in chronic pancreatitis. Trypsin may have direct effects on sensory neurons via the protease-activated receptor 2 (PAR-2).…”

Section: Pathogenesis Of Pain In Chronic Pancreatitismentioning

confidence: 99%

The pain of chronic pancreatitis: a persistent clinical challenge

Goulden

2013

British Journal of Pain

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The pain of chronic pancreatitis represents a major challenge to those working in the field, including pain specialists, gastroenterologists and surgeons. This article describes the different aetiologies of chronic pancreatitis and lists the models for the pathogenesis of pain, including novel ideas such as the role of the immune system in the modulation of pain. The patient profile in chronic pancreatitis is discussed along with the social impact of the disease in relation to alcohol misuse. The range of treatment strategies including medical, endoscopic and surgical approaches are evaluated. Common analgesic regimes and their limitations are reviewed. The pain of chronic pancreatitis remains refractory to effective treatment in many cases and further study and understanding of the underlying pathophysiology are required.

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“…Increased expression of TRPV1 in DRG is evident in this model, as well as in a TNBS colitis model [82], suggesting that TRPV1 up-regulation may be a mechanism by which the effect of a TRPV1 antagonist becomes manifest. This mechanism was also evident In a model of pancreatic inflammation [83]. The up-regulation of function via TRPV1 can be long-term, and may lead to cascades of events resulting in hypersensitivity [81,82].…”

Section: Changes In Sensory Signalling In Diseasementioning

confidence: 79%

TRP Channels in Visceral Pain

Blackshaw¹,

Brierley²,

Harrington³

et al. 2013

TOPAINJ

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Visceral pain is both different and similar to somatic pain - different in being poorly localized and usually referred elsewhere to the body wall, but similar in many of the molecular mechanisms it employs (like TRP channels) and the specialization of afferent endings to detect painful stimuli. TRPV1 is sensitive to low pH. pH is lowest in gastric juice, which may cause severe pain when exposed to the oesophageal mucosa, and probably works via TRPV1. TRPV1 is found in afferent fibres throughout the viscera, and the TRPV1 agonist capsaicin can recapitulate symptoms experienced in disease. TRPV1 is also involved in normal mechanosensory function in the gut. Roles for TRPV4 and TRPA1 have also been described in visceral afferents, and TRPV4 is highly enriched in them, where it plays a major role in both mechanonociception and chemonociception. It may provide a visceral-specific nociceptor target for drug development. TRPA1 is also involved in mechano-and chemosensory function, but not as selectively as TRPV4. TRPA1 is colocalized with TRPV1 in visceral afferents, where they influence each other's function. Another modulator of TRPV1 is the cool/mint receptor TRPM8, which, when activated can abrogate responses mediated via TRPV1, suggesting that TRPM8 agonists may provide analgesia via this pathway. In all, the viscera are rich in TRP channel targets on nociceptive neurones which we hope will provide opportunities for therapeutic analgesia.

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Transient Receptor Potential Vanilloid 1 Mediates Hyperalgesia and Is Up-Regulated in Rats With Chronic Pancreatitis

Cited by 120 publications

References 47 publications

Activation of TRPV1 Contributes to Morphine Tolerance: Involvement of the Mitogen-Activated Protein Kinase Signaling Pathway

Activation of TRPV1 Contributes to Morphine Tolerance: Involvement of the Mitogen-Activated Protein Kinase Signaling Pathway

The pain of chronic pancreatitis: a persistent clinical challenge

TRP Channels in Visceral Pain

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