Chapter 12. Signal transduction in nociceptive afferent neurons in inflammatory conditions

Bevan, Stuart

doi:10.1016/s0079-6123(08)61089-4

Cited by 11 publications

(6 citation statements)

References 74 publications

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“…It seems possible that ASIC-␤ mediates currents that contribute to the fast proton-activated current in sensory neurons. DRASICmediated currents are slow and sustained (10), similar to the sustained pH-mediated currents recorded from DRG neurons (7,26). However, we found that, in addition to DRG, transcripts for DRASIC were also present, albeit at lower levels, in superior cervical ganglia, spinal cord, and brain stem, where sustained proton-evoked currents have not been described.…”

Section: Discussionsupporting

confidence: 75%

“…5). ASIC-␤-mediated currents thus exhibit similar properties to the native fast pH-evoked current recorded from voltageclamped DRG neurons in response to low pH (26). It seems possible that ASIC-␤ mediates currents that contribute to the fast proton-activated current in sensory neurons.…”

Section: Discussionmentioning

confidence: 57%

“…This region is presumably not present in the DRASIC channel because amiloride produces potentiation of currents passing through this channel (10). It has been suggested that the selective neurotoxin capsaicin and protons may activate the same channel in sensory neurons (26). The recent molecular cloning of the capsaicin-gated channel VR1 suggests that this is not the case because VR1-mediated currents were reported not to be activated by low pH (27).…”

Section: Discussionmentioning

confidence: 99%

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A sensory neuron-specific, proton-gated ion channel

Chen

England

Akopian

et al. 1998

Proc. Natl. Acad. Sci. U.S.A.

420

333

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Proton-gated channels expressed by sensory neurons are of particular interest because low pH causes pain. Two proton-gated channels, acid-sensing ionic channel (ASIC) and dorsal root ASIC (DRASIC), that are members of the amiloride-sensitive ENaC͞Degenerin family are known to be expressed by sensory neurons. Here, we describe the cloning and characterization of an ASIC splice variant, ASIC-␤, which contains a unique N-terminal 172 aa, as well as unique 5 and 3 untranslated sequences. ASIC-␤, unlike ASIC and DRASIC, is found only in a subset of small and large diameter sensory neurons and is absent from sympathetic neurons or the central nervous system. The patterns of expression of ASIC and ASIC-␤ transcripts in rat dorsal root ganglion neurons are distinct. When expressed in COS-7 cells, ASIC-␤ forms a functional channel with electrophysiological properties distinct from ASIC and DRASIC. The pH dependency and sensitivity to amiloride of ASIC-␤ is similar to that described for ASIC, but unlike ASIC, the channel is not permeable to calcium, nor are ASIC-␤-mediated currents inhibited by extracellular calcium. The unique distribution of ASIC-␤ suggests that it may play a specialized role in sensory neuron function.

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Section: Discussionsupporting

confidence: 75%

Section: Discussionmentioning

confidence: 57%

Section: Discussionmentioning

confidence: 99%

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A sensory neuron-specific, proton-gated ion channel

Chen

England

Akopian

et al. 1998

Proc. Natl. Acad. Sci. U.S.A.

420

333

View full text Add to dashboard Cite

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“…We chose to use cultured DRGs as model nociceptors to minimize the amount of venom required for each experiment. Lack of nerve growth factor in culture medium is known to lead to the progressive loss of proton and capsaicin sensitivities over several days (Bevan 1996). Therefore we used the cultured DRGs within 6 -24 h of plating, and, accordingly, the proton and capsaicin sensitivities remained robust.…”

Section: Discussionmentioning

confidence: 99%

Venom From the Platypus,Ornithorhynchus anatinus,Induces a Calcium-Dependent Current in Cultured Dorsal Root Ganglion Cells

Plater

Milburn

Martin

2001

Journal of Neurophysiology

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The platypus (Ornithorhynchus anatinus), a uniquely Australian species, is one of the few living venomous mammals. Although envenomation of humans by many vertebrate and invertebrate species results in pain, this is often not the principal symptom of envenomation. However, platypus envenomation results in an immediate excruciating pain that develops into a very long-lasting hyperalgesia. We have previously shown that the venom contains a C-type natriuretic peptide that causes mast cell degranulation, and this probably contributes to the development of the painful response. Now we demonstrate that platypus venom has a potent action on putative nociceptors. Application of the venom to small to medium diameter dorsal root ganglion cells for 10 s resulted in an inward current lasting several minutes when the venom was diluted in buffer at pH 6.1 but not at pH 7.4. The venom itself has a pH of 6.3. The venom activated a current with a linear current-voltage relationship between -100 and -25 mV and with a reversal potential of -11 mV. Ion substitution experiments indicate that the current is a nonspecific cationic current. The response to the venom was blocked by the membrane-permeant Ca(2+)-ATPase inhibitor, thapsigargin, and by the tyrosine- and serine-kinase inhibitor, k252a. Thus the response appears to be dependent on calcium release from intracellular stores. The identity of the venom component(s) that is responsible for the responses we have described is yet to be determined but is probably not the C-type natriuretic peptide or the defensin-like peptides that are present in the venom.

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“…The mediators activate second messenger cascades, which then influence ion channels in the membrane. This process leads to enhanced excitability of the neuron, with lowered threshold and increased action potential frequency elicited during suprathreshold stimulation [18]. Up to now, drug treatment interferes only with the synthesis of prostaglandins (see below) but many other important molecules are not directly targeted.…”

Section: Peripheral Mechanisms Of Pathophysiological Nociceptive Painmentioning

confidence: 99%

Pathophysiology of pain

Schaible

Richter

2004

Langenbecks Arch Surg

131

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Pain is a major symptom of many different diseases. Modern pain research has uncovered important neuronal mechanisms that are underlying clinically relevant pain states, and research goes on to define different types of pains on the basis of their neuronal and molecular mechanisms. This review will briefly outline neuronal mechanisms of pathophysiological nociceptive pain resulting from inflammation and injury, and neuropathic pain resulting from nerve damage. Pain is the sensation that is specifically evoked by potential or actual noxious (i.e. tissue damaging) stimuli or by tissue injury. Pain research has not only explored the neuronal and molecular basis of the "pain system" of the healthy subject but has also provided insights into the function and plasticity of the "pain system" during clinically relevant pains such as post-injury pain, inflammatory pain, postoperative pain, cancer pain and neuropathic pain. This review will briefly describe the "pain system" and then address neuronal mechanisms that are involved in clinical pain states.

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Chapter 12. Signal transduction in nociceptive afferent neurons in inflammatory conditions

Cited by 11 publications

References 74 publications

A sensory neuron-specific, proton-gated ion channel

A sensory neuron-specific, proton-gated ion channel

Venom From the Platypus,Ornithorhynchus anatinus,Induces a Calcium-Dependent Current in Cultured Dorsal Root Ganglion Cells

Pathophysiology of pain

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