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Article ; Online: TRPV1: A Common Denominator Mediating Antinociceptive and Antiemetic Effects of Cannabinoids.

Louis-Gray, Kathleen / Tupal, Srinivasan / Premkumar, Louis S

International journal of molecular sciences

2022 Volume 23, Issue 17

Abstract: The most common medicinal claims for cannabis are relief from chronic pain, stimulation of appetite, and as an antiemetic. However, the mechanisms by which cannabis reduces pain and prevents nausea and vomiting are not fully understood. Among more than ... ...

Abstract	The most common medicinal claims for cannabis are relief from chronic pain, stimulation of appetite, and as an antiemetic. However, the mechanisms by which cannabis reduces pain and prevents nausea and vomiting are not fully understood. Among more than 450 constituents in cannabis, the most abundant cannabinoids are Δ
MeSH term(s)	Analgesics/pharmacology ; Analgesics/therapeutic use ; Antiemetics ; Cannabinoids/pharmacology ; Cannabinoids/therapeutic use ; Humans ; Nausea ; Pain/metabolism ; Solitary Nucleus/metabolism ; TRPV Cation Channels/metabolism ; Transient Receptor Potential Channels/metabolism ; Vomiting/chemically induced ; Vomiting/drug therapy
Chemical Substances	Analgesics ; Antiemetics ; Cannabinoids ; TRPV Cation Channels ; TRPV1 protein, human ; Transient Receptor Potential Channels
Language	English
Publishing date	2022-09-02
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms231710016
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Article ; Online: TRPV1

Kathleen Louis-Gray / Srinivasan Tupal / Louis S. Premkumar

International Journal of Molecular Sciences, Vol 23, Iss 10016, p

A Common Denominator Mediating Antinociceptive and Antiemetic Effects of Cannabinoids

2022 Volume 10016

Abstract	The most common medicinal claims for cannabis are relief from chronic pain, stimulation of appetite, and as an antiemetic. However, the mechanisms by which cannabis reduces pain and prevents nausea and vomiting are not fully understood. Among more than 450 constituents in cannabis, the most abundant cannabinoids are Δ 9 -tetrahydrocannabinol (THC) and cannabidiol (CBD). Cannabinoids either directly or indirectly modulate ion channel function. Transient receptor potential vanilloid 1 (TRPV1) is an ion channel responsible for mediating several modalities of pain, and it is expressed in both the peripheral and the central pain pathways. Activation of TRPV1 in sensory neurons mediates nociception in the ascending pain pathway, while activation of TRPV1 in the central descending pain pathway, which involves the rostral ventral medulla (RVM) and the periaqueductal gray (PAG), mediates antinociception. TRPV1 channels are thought to be implicated in neuropathic/spontaneous pain perception in the setting of impaired descending antinociceptive control. Activation of TRPV1 also can cause the release of calcitonin gene-related peptide (CGRP) and other neuropeptides/neurotransmitters from the peripheral and central nerve terminals, including the vagal nerve terminal innervating the gut that forms central synapses at the nucleus tractus solitarius (NTS). One of the adverse effects of chronic cannabis use is the paradoxical cannabis-induced hyperemesis syndrome (HES), which is becoming more common, perhaps due to the wider availability of cannabis-containing products and the chronic use of products containing higher levels of cannabinoids. Although, the mechanism of HES is unknown, the effective treatment options include hot-water hydrotherapy and the topical application of capsaicin, both activate TRPV1 channels and may involve the vagal-NTS and area postrema (AP) nausea and vomiting pathway. In this review, we will delineate the activation of TRPV1 by cannabinoids and their role in the antinociceptive/nociceptive and ...
Keywords	cannabinoids ; Δ 9 -tetrahydrocannabinol ; cannabidiol ; TRPV1 ; resiniferatoxin ; antinociception and antiemesis ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	500
Language	English
Publishing date	2022-09-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Role of Mechanoinsensitive Nociceptors in Painful Diabetic Peripheral Neuropathy.

Nemenov, Mikhail I / Singleton, J Robinson / Premkumar, Louis S

Current diabetes reviews

2021 Volume 18, Issue 5, Page(s) e081221198649

Abstract: The cutaneous mechanisms that trigger spontaneous neuropathic pain in diabetic peripheral neuropathy (PDPN) are far from clear. Two types of nociceptors are found within the epidermal and dermal skin layers. Small-diameter lightly myelinated Aδ and ... ...

Abstract	The cutaneous mechanisms that trigger spontaneous neuropathic pain in diabetic peripheral neuropathy (PDPN) are far from clear. Two types of nociceptors are found within the epidermal and dermal skin layers. Small-diameter lightly myelinated Aδ and unmyelinated C cutaneous mechano and heat-sensitive (AMH and CMH) and C mechanoinsensitive (CMi) nociceptors transmit pain from the periphery to central nervous system. AMH and CMH fibers are mainly located in the epidermis, and CMi fibers are distributed in the dermis. In DPN, dying back intra-epidermal AMH and CMH fibers leads to reduced pain sensitivity, and the patients exhibit significantly increased pain thresholds to acute pain when tested using traditional methods. The role of CMi fibers in painful neuropathies has not been fully explored. Microneurography has been the only tool to access CMi fibers and differentiate AMH, CMH, and CMi fiber types. Due to the complexity, its use is impractical in clinical settings. In contrast, a newly developed diode laser fiber selective stimulation (DLss) technique allows to safely and selectively stimulate Aδ and C fibers in the superficial and deep skin layers. DLss data demonstrate that patients with painful DPN have increased Aδ fiber pain thresholds, while C-fiber thresholds are intact because, in these patients, CMi fibers are abnormally spontaneously active. It is also possible to determine the involvement of CMi fibers by measuring the area of DLss-induced neurogenic axon reflex flare. The differences in AMH, CMH, and CMi fibers identify patients with painful and painless neuropathy. In this review, we will discuss the role of CMi fibers in PDPN.
MeSH term(s)	Diabetes Mellitus ; Diabetic Neuropathies ; Humans ; Nerve Fibers, Unmyelinated/physiology ; Nociceptors/physiology ; Pain ; Skin
Language	English
Publishing date	2021-12-07
Publishing country	United Arab Emirates
Document type	Journal Article ; Review
ISSN	1875-6417
ISSN (online)	1875-6417
DOI	10.2174/1573399818666211208101555
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Article ; Online: Evaluation of a polymer-coated nanoparticle cream formulation of resiniferatoxin for the treatment of painful diabetic peripheral neuropathy.

Baskaran, Padmamalini / Mohandass, Adithya / Gustafson, Noah / Bennis, Jane / Louis, Somaja / Alexander, Brenda / Nemenov, Mikhail I / Thyagarajan, Baskaran / Premkumar, Louis S

Pain

2022 Volume 164, Issue 4, Page(s) 782–790

Abstract: Abstract: Painful diabetic peripheral neuropathy (PDPN) is one of the major complications of diabetes. Currently, centrally acting drugs and topical analgesics are used for treating PDPN. These drugs have adverse effects; some are ineffective, and ... ...

Abstract	Abstract: Painful diabetic peripheral neuropathy (PDPN) is one of the major complications of diabetes. Currently, centrally acting drugs and topical analgesics are used for treating PDPN. These drugs have adverse effects; some are ineffective, and treatment with opioids is associated with use dependence and addiction. Recent research indicates that transient receptor potential vanilloid 1 (TRPV1) expressed in the peripheral sensory nerve terminals is an emerging target to treat pain associated with PDPN. Block of TRPV1 ion channel with specific antagonists, although effective as an analgesic, induced hyperthermia in clinical trials. However, TRPV1 agonists are useful to treat pain by virtue of their ability to cause Ca 2+ influx and subsequently leading to nerve terminal desensitization. Here, we report the effectiveness of an ultrapotent TRPV1 agonist, resiniferatoxin (RTX) nanoparticle, in a topical formulation (RTX-cream; RESINIZIN) that alleviates pain associated with DPN in animal models of diabetes. Resiniferatoxin causes nerve terminal depolarization block in the short term, which prevents pain during application and leading to nerve terminal desensitization/depletion in the long term resulting in long-lasting pain relief. Application of RTX cream to the hind limbs suppresses thermal hyperalgesia in streptozotocin-induced diabetic rats and mini pigs without any adverse effects as compared with capsaicin at therapeutic doses, which induces intense pain during application. Resiniferatoxin cream also decreases the expression of TRPV1 in the peripheral nerve endings and suppresses TRPV1-mediated calcitonin gene-related peptide release in the skin samples of diabetic rats and mini pigs. Our preclinical data confirm that RTX topical formulation is an effective treatment option for PDPN.
MeSH term(s)	Swine ; Rats ; Animals ; Diabetic Neuropathies/drug therapy ; Diabetes Mellitus, Experimental/complications ; Diabetes Mellitus, Experimental/drug therapy ; Swine, Miniature/metabolism ; Pain ; Diterpenes/therapeutic use ; Analgesics/therapeutic use ; Capsaicin/pharmacology ; TRPV Cation Channels/metabolism
Chemical Substances	resiniferatoxin (A5O6P1UL4I) ; Diterpenes ; Analgesics ; Capsaicin (S07O44R1ZM) ; TRPV Cation Channels
Language	English
Publishing date	2022-08-24
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	193153-2
ISSN	1872-6623 ; 0304-3959
ISSN (online)	1872-6623
ISSN	0304-3959
DOI	10.1097/j.pain.0000000000002765
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Article ; Online: Transient receptor potential channels as targets for phytochemicals.

Premkumar, Louis S

ACS chemical neuroscience

2014 Volume 5, Issue 11, Page(s) 1117–1130

Abstract: To date, 28 mammalian transient receptor potential (TRP) channels have been cloned and characterized. They are grouped into six subfamilies on the basis of their amino acid sequence homology: TRP Ankyrin (TRPA), TRP Canonical (TRPC), TRP Melastatin (TRPM) ...

Abstract	To date, 28 mammalian transient receptor potential (TRP) channels have been cloned and characterized. They are grouped into six subfamilies on the basis of their amino acid sequence homology: TRP Ankyrin (TRPA), TRP Canonical (TRPC), TRP Melastatin (TRPM), TRP Mucolipin (TRPML), TRP Polycystin (TRPP), and TRP Vanilloid (TRPV). Most of the TRP channels are nonselective cation channels expressed on the cell membrane and exhibit variable permeability ratios for Ca(2+) versus Na(+). They mediate sensory functions (such as vision, nociception, taste transduction, temperature sensation, and pheromone signaling) and homeostatic functions (such as divalent cation flux, hormone release, and osmoregulation). Significant progress has been made in our understanding of the specific roles of these TRP channels and their activation mechanisms. In this Review, the emphasis will be on the activation of TRP channels by phytochemicals that are claimed to exert health benefits. Recent findings complement the anecdotal evidence that some of these phytochemicals have specific receptors and the activation of which is responsible for the physiological effects. Now, the targets for these phytochemicals are being unveiled; a specific hypothesis can be proposed and tested experimentally to infer a scientific validity of the claims of the health benefits. The broader and pressing issues that have to be addressed are related to the quantities of the active ingredients in a given preparation, their bioavailability, metabolism, adverse effects, excretion, and systemic versus local effects.
MeSH term(s)	Animals ; Humans ; Phytochemicals/chemistry ; Phytochemicals/pharmacology ; Transient Receptor Potential Channels/drug effects ; Transient Receptor Potential Channels/metabolism
Chemical Substances	Phytochemicals ; Transient Receptor Potential Channels
Language	English
Publishing date	2014-06-24
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Review
ISSN	1948-7193
ISSN (online)	1948-7193
DOI	10.1021/cn500094a
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Article ; Online: Role of Transient Receptor Potential Channels Trpv1 and Trpm8 in Diabetic Peripheral Neuropathy.

Pabbidi, Mallikarjuna R / Premkumar, Louis S

Journal of diabetes and treatment

2017 Volume 2017, Issue 4

Abstract: Objective: 1.1.Transient Receptor Potential (Vanilloid 1) TRPV1 and (Melastatin 8) TRPM8 are heat and cold sensing non-selective cation channels, respectively. We sought to correlate the modulation of TRPV1- and TRPM8-mediated membrane currents and ... ...

Abstract	Objective: 1.1.Transient Receptor Potential (Vanilloid 1) TRPV1 and (Melastatin 8) TRPM8 are heat and cold sensing non-selective cation channels, respectively. We sought to correlate the modulation of TRPV1- and TRPM8-mediated membrane currents and altered thermal sensitivity in Diabetic Peripheral Neuropathy (DPN). Method: 1.2.Streptozotocin (STZ)-induced diabetic mice were used and thermal (heat and cold) pain sensitivities were determined using hot plate and acetone drop test, respectively. Membrane currents were recorded using patch-clamp techniques. Results: 1.3.First, we tested thermal pain sensitivities to implicate a possible role of TRPV1 and TRPM8 in DPN. Paw withdrawal latency on a hot plate test was decreased, and acetone-induced cold sensitivity was enhanced in diabetic mice as compared to non-diabetic mice. Dorsal Root Ganglion (DRG) neurons dissociated from diabetic hyperalgesic mice exhibited an increase in TRPV1-mediated current and a decrease in TRPM8-mediated currents as compared to non-diabetic mice. Then, we determined the modulation of TRPV1- and TRPM8-mediated currents using HEK cells heterologously expressing TRPV1 by promoting PKC- and PKA-mediated phosphorylation. Both Phorbol 12,13-Dibutyrate (PDBu), a PKC activator and forskolin, a PKA activator upregulated TRPV1-mediated currents but downregulated TRPM8-mediated currents. In diabetic mice, intraplantar injection of capsaicin, a TRPV1 agonist-induced nocifensive behavior but the severity of this behavior was significantly lower when co-administered with menthol, a TRPM8 agonist. Conclusions: 1.4.These findings suggest that diabetic thermal hyperalgesia mediated by up-regulation of TRPV1 function may be further aggravated by the downregulation of TRPM8 function. Targeting TRPV1 may be a useful approach to alleviate pain associated with DPN.
Language	English
Publishing date	2017-10-17
Publishing country	United States
Document type	Journal Article
ISSN	2574-7568
ISSN (online)	2574-7568
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Expression and Function of Transient Receptor Potential Ankyrin 1 Ion Channels in the Caudal Nucleus of the Solitary Tract.

Feng, Lin / Uteshev, Victor V / Premkumar, Louis S

International journal of molecular sciences

2019 Volume 20, Issue 9

Abstract: The nucleus of the solitary tract (NTS) receives visceral information via the solitary tract (ST) that comprises the sensory components of the cranial nerves VII, IX and X. The Transient Receptor Potential Ankyrin 1 (TRPA1) ion channels are non-selective ...

Abstract	The nucleus of the solitary tract (NTS) receives visceral information via the solitary tract (ST) that comprises the sensory components of the cranial nerves VII, IX and X. The Transient Receptor Potential Ankyrin 1 (TRPA1) ion channels are non-selective cation channels that are expressed primarily in pain-related sensory neurons and nerve fibers. Thus, TRPA1 expressed in the primary sensory afferents may modulate the function of second order NTS neurons. This hypothesis was tested and confirmed in the present study using acute brainstem slices and caudal NTS neurons by RT-PCR, immunostaining and patch-clamp electrophysiology. The expression of TRPA1 was detected in presynaptic locations, but not the somata of caudal NTS neurons that did not express TRPA1 mRNA or proteins. Moreover, caudal NTS neurons did not show somatodendritic responsiveness to TRPA1 agonists, while TRPA1 immunostaining was detected only in the afferent fibers. Electrophysiological recordings detected activation of presynaptic TRPA1 in glutamatergic terminals synapsing on caudal NTS neurons evidenced by the enhanced glutamatergic synaptic neurotransmission in the presence of TRPA1 agonists. The requirement of TRPA1 for modulation of spontaneous synaptic activity was confirmed using TRPA1 knockout mice where TRPA1 agonists failed to alter synaptic efficacy. Thus, this study provides the first evidence of the TRPA1-dependent modulation of the primary afferent inputs to the caudal NTS. These results suggest that the second order caudal NTS neurons act as a TRPA1-dependent interface for visceral noxious-innocuous integration at the level of the caudal brainstem.
MeSH term(s)	Animals ; Ankyrins/genetics ; Ankyrins/metabolism ; Immunohistochemistry ; Male ; Mice ; Rats ; Rats, Sprague-Dawley ; Reverse Transcriptase Polymerase Chain Reaction ; Solitary Nucleus/metabolism ; Synaptic Transmission/genetics ; Synaptic Transmission/physiology ; TRPA1 Cation Channel/genetics ; TRPA1 Cation Channel/metabolism
Chemical Substances	Ankyrins ; TRPA1 Cation Channel
Language	English
Publishing date	2019-04-26
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms20092065
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Article ; Online: Expression and Function of Transient Receptor Potential Ankyrin 1 Ion Channels in the Caudal Nucleus of the Solitary Tract

Lin Feng / Victor V. Uteshev / Louis S. Premkumar

International Journal of Molecular Sciences, Vol 20, Iss 9, p

2019 Volume 2065

Abstract	The nucleus of the solitary tract (NTS) receives visceral information via the solitary tract (ST) that comprises the sensory components of the cranial nerves VII, IX and X. The Transient Receptor Potential Ankyrin 1 (TRPA1) ion channels are non-selective cation channels that are expressed primarily in pain-related sensory neurons and nerve fibers. Thus, TRPA1 expressed in the primary sensory afferents may modulate the function of second order NTS neurons. This hypothesis was tested and confirmed in the present study using acute brainstem slices and caudal NTS neurons by RT-PCR, immunostaining and patch-clamp electrophysiology. The expression of TRPA1 was detected in presynaptic locations, but not the somata of caudal NTS neurons that did not express TRPA1 mRNA or proteins. Moreover, caudal NTS neurons did not show somatodendritic responsiveness to TRPA1 agonists, while TRPA1 immunostaining was detected only in the afferent fibers. Electrophysiological recordings detected activation of presynaptic TRPA1 in glutamatergic terminals synapsing on caudal NTS neurons evidenced by the enhanced glutamatergic synaptic neurotransmission in the presence of TRPA1 agonists. The requirement of TRPA1 for modulation of spontaneous synaptic activity was confirmed using TRPA1 knockout mice where TRPA1 agonists failed to alter synaptic efficacy. Thus, this study provides the first evidence of the TRPA1-dependent modulation of the primary afferent inputs to the caudal NTS. These results suggest that the second order caudal NTS neurons act as a TRPA1-dependent interface for visceral noxious-innocuous integration at the level of the caudal brainstem.
Keywords	ion channel ; transient receptor potential ankyrin 1 (TRPA1) ; synaptic transmission ; nucleus tractus solitarius (NTS) ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	571
Language	English
Publishing date	2019-04-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Targeting TRPV1 as an alternative approach to narcotic analgesics to treat chronic pain conditions.

Premkumar, Louis S

The AAPS journal

2010 Volume 12, Issue 3, Page(s) 361–370

Abstract: In spite of intense research efforts and after the dedicated Decade of Pain Control and Research, there are not many alternatives to opioid-based narcotic analgesics in the therapeutic armamentarium to treat chronic pain conditions. Chronic opioid ... ...

Abstract	In spite of intense research efforts and after the dedicated Decade of Pain Control and Research, there are not many alternatives to opioid-based narcotic analgesics in the therapeutic armamentarium to treat chronic pain conditions. Chronic opioid treatment is associated with sedation, tolerance, dependence, hyperalgesia, respiratory depression, and constipation. Since the affective component is an integral part of pain perception, perhaps it is inevitable that potent analgesics possess the property of impacting pain pathways in the supraspinal structures. The question still remains to be answered is that whether a powerful analgesic can be devoid of narcotic effect and addictive potentials. Local anesthetics are powerful analgesics for acute pain by blocking voltage-gated sodium channels that are involved in generation and propagation of action potentials. Antidepressants and anticonvulsants have proven to be useful in the treatment of certain modalities of pain. In neuropathic pain conditions, the complexity arises because of the notion that neuronal circuitry is altered, as occurs in phantom pain, in that pain is perceived even in the absence of peripheral nociceptive inputs. If the locus of these changes is in the central nervous system, commonly used analgesics may not be very useful. This review focuses on the recent advances in nociceptive transmission and nociceptive transient receptor potential vanilloid 1 channel as a target for treating chronic pain conditions with its agonists/antagonists.
MeSH term(s)	Analgesics, Opioid/pharmacology ; Analgesics, Opioid/therapeutic use ; Chronic Disease ; Humans ; Pain/drug therapy ; Pain/physiopathology ; TRPV Cation Channels/drug effects
Chemical Substances	Analgesics, Opioid ; TRPV Cation Channels ; TRPV1 protein, human
Language	English
Publishing date	2010-05-04
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ISSN	1550-7416
ISSN (online)	1550-7416
DOI	10.1208/s12248-010-9196-y
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Article ; Online: Neuropathic pain-induced enhancement of spontaneous and pain-evoked neuronal activity in the periaqueductal gray that is attenuated by gabapentin.

Samineni, Vijay K / Premkumar, Louis S / Faingold, Carl L

Pain

2017 Volume 158, Issue 7, Page(s) 1241–1253

Abstract: Neuropathic pain is a debilitating pathological condition that is poorly understood. Recent evidence suggests that abnormal central processing occurs during the development of neuropathic pain induced by the cancer chemotherapeutic agent, paclitaxel. Yet, ...

Abstract	Neuropathic pain is a debilitating pathological condition that is poorly understood. Recent evidence suggests that abnormal central processing occurs during the development of neuropathic pain induced by the cancer chemotherapeutic agent, paclitaxel. Yet, it is unclear what role neurons in supraspinal pain network sites, such as the periaqueductal gray, play in altered behavioral sensitivity seen during chronic pain conditions. To elucidate these mechanisms, we studied the spontaneous and thermally evoked firing patterns of ventrolateral periaqueductal gray (vlPAG) neurons in awake-behaving rats treated with paclitaxel to induce neuropathic pain. In the present study, vlPAG neurons in naive rats exhibited either excitatory, inhibitory, or neutral responses to noxious thermal stimuli, as previously observed. However, after development of behavioral hypersensitivity induced by the chemotherapeutic agent, paclitaxel, vlPAG neurons displayed increased neuronal activity and changes in thermal pain-evoked neuronal activity. This involved elevated levels of spontaneous firing and heightened responsiveness to nonnoxious stimuli (allodynia) as well as noxious thermal stimuli (hyperalgesia) as compared with controls. Furthermore, after paclitaxel treatment, only excitatory neuronal responses were observed for both nonnoxious and noxious thermal stimuli. Systemic administration of gabapentin, a nonopioid analgesic, induced significant dose-dependent decreases in the elevated spontaneous and thermally evoked vlPAG neuronal firing to both nonnoxious and noxious thermal stimuli in rats exhibiting neuropathic pain, but not in naive rats. Thus, these results show a strong correlation between behavioral hypersensitivity to thermal stimuli and increased firing of vlPAG neurons in allodynia and hyperalgesia that occur in this neuropathic pain model.
MeSH term(s)	Action Potentials/drug effects ; Action Potentials/physiology ; Amines/pharmacology ; Amines/therapeutic use ; Analgesics/pharmacology ; Analgesics/therapeutic use ; Animals ; Cyclohexanecarboxylic Acids/pharmacology ; Cyclohexanecarboxylic Acids/therapeutic use ; Gabapentin ; Hot Temperature ; Male ; Neuralgia/chemically induced ; Neuralgia/drug therapy ; Neuralgia/physiopathology ; Neuronal Plasticity/drug effects ; Neuronal Plasticity/physiology ; Neurons/drug effects ; Neurons/physiology ; Paclitaxel ; Periaqueductal Gray/drug effects ; Periaqueductal Gray/physiopathology ; Rats ; Rats, Sprague-Dawley ; gamma-Aminobutyric Acid/pharmacology ; gamma-Aminobutyric Acid/therapeutic use
Chemical Substances	Amines ; Analgesics ; Cyclohexanecarboxylic Acids ; gamma-Aminobutyric Acid (56-12-2) ; Gabapentin (6CW7F3G59X) ; Paclitaxel (P88XT4IS4D)
Language	English
Publishing date	2017-03-17
Publishing country	United States
Document type	Journal Article
ZDB-ID	193153-2
ISSN	1872-6623 ; 0304-3959
ISSN (online)	1872-6623
ISSN	0304-3959
DOI	10.1097/j.pain.0000000000000905
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