Differences between nerve terminal impulses of polymodal nociceptors and cold sensory receptors of the guinea‐pig cornea

Brock, James A.; Pianova, Svetlana; Belmonte, Carlos

doi:10.1111/j.1469-7793.2001.0493a.x

Cited by 75 publications

(92 citation statements)

References 15 publications

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“…Our work in the isolated cornea confirms previous studies showing that this tissue is innervated by cold-and mentholsensitive sensory fibers (Gallar et al, 1993;Brock et al, 2001;Acosta et al, 2001;Carr et al, 2003) that exhibit rhythmic ongoing activity and response characteristics typical of innocuous cold receptor fibers previously described in the trigeminal territory (Hensel and Wurster, 1970;Schafer et al, 1988). BCTC did not affect the spontaneous activity of corneal cold receptor endings.…”

Section: Specific Effects Of Bctc On Trpm8 Channelssupporting

confidence: 91%

“…Data were captured and analyzed using a CED 1401 interface coupled to a computer running Spike 2 software (Cambridge Electronics Design, Cambridge, UK). Only NTIs originating from single cold-sensitive receptors were recorded, identifiable by their relatively high level of spontaneous discharge (in this study, 4 -15 Hz), sometimes in a bursting pattern, which was increased by cooling and decreased by warming of the superfusion solution (Brock et al, 1998(Brock et al, , 2001.…”

Section: Methodsmentioning

confidence: 92%

“…The transduction of temperature stimuli into propagated nerve impulses occurs in free endings of thin sensory axons (Hensel and Zotterman, 1951;Hensel, 1981;Heppelmann et al, 1990). At normal skin temperatures, innocuous cold thermoreceptors exhibit spontaneous, periodic activity that is augmented by cooling and silenced by warming (Hensel and Zotterman, 1951;Brock et al, 2001). In contrast, cold nociceptors are quiescent at rest firing only in response to low temperatures (LaMotte and Thalhammer, 1982;Simone and Kajander, 1997).…”

Section: Introductionmentioning

confidence: 99%

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Contribution of TRPM8 Channels to Cold Transduction in Primary Sensory Neurons and Peripheral Nerve Terminals

Madrid¹,

Donovan-Rodríguez²,

Meseguer³

et al. 2006

J. Neurosci.

154

161

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Transient receptor potential melastatin 8 (TRPM8) is the best molecular candidate for innocuous cold detection by peripheral thermoreceptor terminals. To dissect out the contribution of this cold-and menthol-gated, nonselective cation channel to cold transduction, we identified BCTC [N-(4-tert-butylphenyl)-4-(3-chloropyridin-2-yl)piperazine-1-carboxamide] as a potent and full blocker of recombinant TRPM8 channels. In cold-sensitive trigeminal ganglion neurons of mice and guinea pig, responses to menthol were abolished by BCTC. In contrast, the effect of BCTC on cold-evoked responses was variable but showed a good correlation with the presence or lack of menthol sensitivity in the same neuron, suggesting a specific blocking action of BCTC on TRPM8 channels. The biophysical properties of native cold-gated currents (I cold ), and the currents blocked by BCTC were nearly identical, consistent with a role of this channel in cold sensing at the soma. The temperature activation threshold of native TRPM8 channels was significantly warmer than those reported in previous expression studies. The effect of BCTC on native I cold was characterized by a dose-dependent shift in the temperature threshold of activation.The role of TRPM8 in transduction was further investigated in the guinea pig cornea, a peripheral territory densely innervated with cold thermoreceptors. All cold-sensitive terminals were activated by menthol, suggesting the functional expression of TRPM8 channels in their membrane. However, the spontaneous activity and firing pattern characteristic of cold thermoreceptors was totally immune to TRPM8 channel blockade with BCTC or SKF96365 (1-[2-(4-methoxyphenyl)-2-[3-(4-methoxyphenyl)propoxy]ethyl-1 H-imidazole hydrochloride). Cold-evoked responses in corneal terminals were also essentially unaffected by these drugs, whereas responses to menthol were completely abolished. The minor impairment in the ability to transduce cold stimuli by peripheral corneal thermoreceptors during TRPM8 blockade unveils an overlapping functional role for various thermosensitive mechanisms in these nerve terminals.

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Section: Specific Effects Of Bctc On Trpm8 Channelssupporting

confidence: 91%

Section: Methodsmentioning

confidence: 92%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Contribution of TRPM8 Channels to Cold Transduction in Primary Sensory Neurons and Peripheral Nerve Terminals

Madrid¹,

Donovan-Rodríguez²,

Meseguer³

et al. 2006

J. Neurosci.

154

161

View full text Add to dashboard Cite

show abstract

“…[48][49][50] It has been postulated that action potential firing of cold thermoreceptors originates within a single spatially restricted region of the nerve terminal arbor of the parent axon, where each separate branch encodes individual action potentials autonomously. [51][52][53] Altered architecture of cold terminals and abnormal expression of ion channels involved in cold transduction and coding after injury likely decrease both the transducing membrane surface and the number of membrane points at which propagated impulses may generate. Both circumstances are expected to contribute to the lower background frequency and abnormal firing observed in cold thermoreceptor terminals of the injured cornea after PRK.…”

Section: Discussionmentioning

confidence: 99%

Functional and Morphologic Alterations in Mechanical, Polymodal, and Cold Sensory Nerve Fibers of the Cornea Following Photorefractive Keratectomy

Bech

González-González

Artime

et al. 2018

Invest. Ophthalmol. Vis. Sci.

Self Cite

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PURPOSE. To define the characteristics and time course of the morphologic and functional changes experienced by corneal sensory nerves after photorefractive keratectomy (PRK).METHODS. Unilateral corneal excimer laser photoablation was performed in 54 anesthetized 3-to 6-month-old mice; 11 naïve animals served as control. Mice were killed 0, 3, 7, 15, and 30 days after PRK. Excised eyes were placed in a recording chamber superfused at 348C. Electrical nerve impulse activity of single sensory terminals was recorded with a micropipette applied onto the corneal surface. Spontaneous and stimulus-evoked (cold, heat, mechanical, and chemical stimuli) nerve terminal impulse (NTI) activity was analyzed. Corneas were fixed and stained with anti-b-Tubulin III antibody to measure nerve density and number of epithelial nerve penetration points of regenerating subbasal leashes.RESULTS. Nerve fibers and NTI activity were absent in the injured area between 0 and 7 days after PRK, when sparse regenerating nerve sprouts appear. On day 15, subbasal nerve density reached half the control value and abnormally responding cold-sensitive terminals were recorded inside the lesion. Thirty days after PRK, nerve density was almost restored, active cold thermoreceptors were abundant, and polymodal nociceptor activity first reappeared.CONCLUSIONS. Morphologic regeneration of subbasal corneal nerves started shortly after PRK ablation and was substantially completed 30 days later. Functional recovery appears faster in cold terminals than polymodal terminals, possibly reflecting an incomplete damage of the more extensively branched cold-sensitive axon terminals. Evolution of postsurgical discomfort sensations quality may be associated with the variable regeneration pattern of each fiber type.

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“…68 The TTX-R channels can initiate action potentials in polymodal nociceptive afferents, and because these sites are close to the axon terminals, they also contribute to transmitter release from nociceptive afferents. 63,69 The VGSCs are clearly linked to neuronal excitability, and changes in populations of these channels may enhance the ability of sensory neurons to respond to external stimuli, and may mediate sensitized pain states.…”

Section: Increased Neuronal Excitationmentioning

confidence: 99%

Challenges in the development of novel treatment strategies for neuropathic pain

Ossipov

Porreca

2005

Neurotherapeutics

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Summary:Neuropathic pain might best be considered as a collection of various pain states with a common feature, that being symptoms suggestive of dysfunction of peripheral nerves. The development of therapeutic options for the treatment of neuropathic pain is complicated significantly by several factors. Neuropathic pain may arise from widely diverse etiologies such as physical trauma, disease, infection, or chemotherapy. Symptoms indicative of neuropathic pain may also arise in individuals with no evidence of any type of nerve trauma (idiopathic). Although neuropathic pain is a substantial health care issue, it is relatively uncommon and only occurs in a small fraction (Ͻ10%) of individuals with these initiating factors. Moreover, the efficacy of treatment protocols, even against the same type of symptoms, differ depending on the underlying initiating cause of the neuropathy. Although these observations strongly suggest that there are predisposing factors that may impart susceptibility to the development of neuropathic pain, no common predisposing factors or genetic markers have been satisfactorily identified. Because of these vagaries, treatment of neuropathic pain has been based on trial and error. However, recent progress in the understanding of neurophysiologic changes that accompany peripheral nerve dysfunction indicate that regulation of ion channels that maintain membrane potentials or generate action potentials may provide an important therapeutic approach. Neuropathic pain is accompanied by increased activity of peripheral nociceptors, which is produced in part by changes in levels of specific calcium and sodium channels. The identification of sodium and/or calcium channels subtypes that are expressed almost exclusively on nocicpetors may provide a way of regulating the activity of exaggerated nociceptor function without altering other sensory modalities. Thus, the selective targeting of ion channels may represent a viable therapeutic target for the management of the neuropathic pain state, regardless of etiology.

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Differences between nerve terminal impulses of polymodal nociceptors and cold sensory receptors of the guinea‐pig cornea

Cited by 75 publications

References 15 publications

Contribution of TRPM8 Channels to Cold Transduction in Primary Sensory Neurons and Peripheral Nerve Terminals

Contribution of TRPM8 Channels to Cold Transduction in Primary Sensory Neurons and Peripheral Nerve Terminals

Functional and Morphologic Alterations in Mechanical, Polymodal, and Cold Sensory Nerve Fibers of the Cornea Following Photorefractive Keratectomy

Challenges in the development of novel treatment strategies for neuropathic pain

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