← Back to Search
Ion Channels Involved In Substance P-Mediated Nociception And Antinociception
C. Chang, Bo-yang Jiang, C. Chen
Published 2019 · Chemistry, Medicine
Download PDFAnalyze on Scholarcy
Substance P (SP), an 11-amino-acid neuropeptide, has long been considered an effector of pain. However, accumulating studies have proposed a paradoxical role of SP in anti-nociception. Here, we review studies of SP-mediated nociception and anti-nociception in terms of peptide features, SP-modulated ion channels, and differential effector systems underlying neurokinin 1 receptors (NK1Rs) in differential cell types to elucidate the effect of SP and further our understanding of SP in anti-nociception. Most importantly, understanding the anti-nociceptive SP-NK1R pathway would provide new insights for analgesic drug development.
This paper references
Reactive oxygen species are second messengers of neurokinin signaling in peripheral sensory neurons
J. Linley (2012)
Altered nociception, analgesia and aggression in mice lacking the receptor for substance P
C. Felipe (1998)
Inhibition of Ca2+ and K+ channels in sympathetic neurons by neuropeptides and other ganglionic transmitters
K. Bley (1990)
Identifying the pathways required for coping behaviours associated with sustained pain
T. Huang (2018)
Isolation of a sialogogic peptide from bovine hypothalamic tissue and its characterization as substance P.
M. Chang (1970)
Analgesic activity of substance P in rats: apparent mediation by met-enkephalin release.
J. Naranjo (1982)
Substance P hyperpolarizes vagal sensory neurones of the ferret.
M. Jafri (1996)
Unilateral intramuscular injections of acidic saline produce a bilateral, long‐lasting hyperalgesia
K. Sluka (2001)
Acid mediates a prolonged antinociception via substance P signaling in acid-induced chronic widespread pain
Wei-Nan Chen (2014)
Substance P in the nervous system.
R. Porter (1982)
PKCepsilon-dependent potentiation of TTX-resistant Nav1.8 current by neurokinin-1 receptor activation in rat dorsal root ganglion neurons
C. L. Cang (2009)
Elevated CSF levels of substance P and high incidence of Raynaud phenomenon in patients with fibromyalgia: new features for diagnosis
H. Vaerøy (1988)
The Endogenous Redox Agent L-Cysteine Induces T-Type Ca2+ Channel-Dependent Sensitization of a Novel Subpopulation of Rat Peripheral Nociceptors
M. T. Nelson (2005)
PKCε-dependent potentiation of TTX-resistant Nav1.8 current by neurokinin-1 receptor activation in rat dorsal root ganglion neurons
Chun-Lei Cang (2009)
Pharmacological characterisation of acid-induced muscle allodynia in rats.
A. N. Nielsen (2004)
Protein kinase C is involved in neurokinin receptor modulation of N- and L-type Ca2+ channels in DRG neurons of the adult rat.
A. Sculptoreanu (2003)
Amino-acid sequence of substance P.
M. Chang (1971)
Inhibition of hyperalgesia by ablation of lamina I spinal neurons expressing the substance P receptor.
P. Mantyh (1997)
Differences in the length of the carboxyl terminus mediate functional properties of neurokinin-1 receptor
J. Lai (2008)
The proliferative and antiapoptotic effects of substance P are facilitated by formation of a beta -arrestin-dependent scaffolding complex.
K. Defea (2000)
Neurokinin 2 receptor‐mediated activation of protein kinase C modulates capsaicin responses in DRG neurons from adult rats
A. Sculptoreanu (2008)
Neurotransmitters and CNS disease
T. M. Jessell (1982)
Substance P and somatostatin inhibit calcium channels in rat sympathetic neurons via different G protein pathways.
M. S. Shapiro (1993)
Substance P Sensitizes P2X3 in Nociceptive Trigeminal Neurons
C. Park (2010)
Enhancement of spinothalamic neuron responses to chemical and mechanical stimuli following combined micro-iontophoretic application of n-methyl-d-aspartic acid and substance P
P. Dougherty (1991)
Dual actions of substance P on nociception: possible role of endogenous opioids
R. Frederickson (1978)
KCNQ/M Currents in Sensory Neurons: Significance for Pain Therapy
G. M. Passmore (2003)
Substance P evokes cation currents through TRP channels in HEK293 cells.
E. J. Oh (2003)
Substance P: does it produce analgesia or hyperalgesia?
P. Oehme (1980)
Immune and inflammatory mechanisms in neuropathic pain
G. Moalem (2006)
Alterations in the substance P-induced anti-nociception in the central nervous system of rats after morphine tolerance
Xiao-Guo Dong (2005)
Muscarinic suppression of a novel voltage-sensitive K+ current in a vertebrate neurone
D. Brown (1980)
Tachykinins: receptor to effector.
A. M. Khawaja (1996)
Amino-acid sequence of substance
M. M. Chang (1971)
Species differences in tachykinin receptor distribution: Further evidence that the substance P (NK1) receptor predominates in human brain
M. Rigby (2005)
Pertussis toxin-insensitive G protein mediates substance P-induced inhibition of potassium channels in brain neurons.
Y. Nakajima (1988)
Experimental human muscle pain induced by intramuscular injections of bradykinin, serotonin, and substance P
Vladimir Babenko (1999)
Mechanical and thermal antinociception in rats following systemic administration of mibefradil, a T-type calcium channel blocker
S. Todorovic (2002)
Differential modulation of neurons in the rostral ventromedial medulla by neurokinin-1 receptors.
T. S. Brink (2012)
Actions of substance P on membrane potential and ionic currents in guinea pig stellate ganglion neurons.
R. Gilbert (1998)
Pain, Tenderness, Wheal and Flare Induced by Substance-P, Bradykinin and 5-Hydroxytryptamine in Humans
K. Jensen (1991)
How prevalent is chronic pain
C. Harstall (2003)
Substance P and somatostatin inhibit calcium channels in rat sympathetic
M. S. Shapiro
An unidentified depressor substance in certain tissue extracts
U. S. v. EULER (1931)
Neurokinins inhibit low threshold inactivating K+ currents in capsaicin responsive DRG neurons
A. Sculptoreanu (2009)
Targeting ASIC3 for pain, anxiety, and insulin resistance.
Wei-li Wu (2012)
TRPV1 sensitization mediates postinflammatory visceral pain following acute colitis.
Tamia K. Lapointe (2015)
Three rat preprotachykinin mRNAs encode the neuropeptides substance P and neurokinin A.
J. Krause (1987)
Cloning of a C-terminally truncated NK-1 receptor from guinea-pig nervous system.
Sarah Baker (2003)
Neurokinin-1 Receptor Enhances TRPV1 Activity in Primary Sensory Neurons via PKCε: A Novel Pathway for Heat Hyperalgesia
H. Zhang (2007)
Investigation into species variants in tachykinin NK1 receptors by use of the non‐peptide antagonist, CP‐96,345
I. Beresford (1991)
Animal models of pain: progress and challenges
J. Mogil (2009)
Differential activation of intracellular effector by two isoforms of human neurokinin-1 receptor.
T. Fong (1992)
Neuronal KCNQ potassium channels:physislogy and role in disease
T. Jentsch (2000)
Peptide neurotransmitters activate a cation channel complex of NALCN and UNC-80
Boxun Lu (2009)
Cutaneous stimuli releasing immunoreactive substance P in the dorsal horn of the cat
A. Duggan (1988)
Elevated cerebrospinal fluid levels of substance P in patients with the fibromyalgia syndrome.
I. J. Russell (1994)
Glutamate and substance P coexist in primary afferent terminals in the superficial laminae of spinal cord.
S. De Biasi (1988)
Substance p stimulates the release of met5-enkephalin-Arg6-Phe7 and Met5-enkephalin from rat spinal cord
Jingcheng Tong (1983)
Feed-forward inhibition: a novel cellular mechanism for the analgesic effect of substance P
L. Wu (2005)
Neurotransmitter functions of mammalian tachykinins.
M. Otsuka (1993)
Chronic hyperalgesia induced by repeated acid injections in muscle is abolished by the loss of ASIC3, but not ASIC1
K. Sluka (2003)
Spinal cord mechanisms mediating behavioral hyperalgesia induced by neurokinin-1 tachykinin receptor activation in the rostral ventromedial medulla
S. C. Lagraize (2010)
Slow excitatory transmission in rat dorsal horn: possible mediation by peptides
L. Urbán (1984)
Biological activity of C-terminal partial sequences of substance P.
R. Bury (1976)
Substance P Decreases the Non‐Selective Cation Channel Conductance in Dissociated Outer Hair Cells of Guinea Pig Cochlea
S. Kakehata (1993)
Human substance P receptor expressed in Chinese hamster ovary cells directly activates G(alpha q/11), G(alpha s), G(alpha o).
E. Roush (1998)
Visceral Pain evoked by Intra-Arterial Injection of Substance P
G. Potter (1962)
Substance P modulates glutamate-induced currents in acutely isolated rat spinal dorsal horn neurones
M. Randić (1990)
Gq/11 and PLC-beta 1 mediate the substance P-induced inhibition of an inward rectifier K+ channel in brain neurons.
K. Takano (1996)
via different G protein pathways
K. R. Bley (1993)
Antagonists that demonstrate species differences in neurokinin-1 receptors.
K. Appell (1992)
Characteristics of dorsal root ganglia neurons sensitive to Substance P
E. R. Moraes (2014)
Primary afferent tachykinins are required to experience moderate to intense pain
Yu Cao (1998)
Intrathecal substance P augments morphine-induced antinociception: Possible relevance in the production of substance P N-terminal fragments
T. Komatsu (2009)
A peripherally acting, selective T-type calcium channel blocker, ABT-639, effectively reduces nociceptive and neuropathic pain in rats.
M. Jarvis (2014)
Substance P-mediated slow excitatory postsynaptic potential elicited in dorsal horn neurons in vivo by noxious stimulation.
Y. de Koninck (1991)
Neurogenic vasodilatation and plasma leakage in the skin.
P. Holzer (1998)
Substance P equals pain substance? Nature
L Iversen (1998)
Substance P in nociceptive sensory neurons.
T. Jessell (1982)
Chemical cross-linking of the substance P (NK-1) receptor to the alpha subunits of the G proteins Gq and G11.
S. Macdonald (1996)
Human substance P receptor expressed in Chinese hamster ovary cells directly activates Gαq/11, Gαs, and Gαo
E. Roush (1998)
Neurokinin 1 Receptors Trigger Overlapping Stimulation and Inhibition of CaV2.3 (R-Type) Calcium Channels
Ulises Meza (2007)
Supraspinal injection of Substance P attenuates allodynia and hyperalgesia in a rat model of inflammatory pain
C. Parenti (2012)
Amino-acid sequence of substance P. Nat
M M Chang (1971)
Species differences in affinities of non-peptide antagonists for substance P receptors.
B. Gitter (1991)
Can We Distinguish between Inflammatory and Neuropathic Pain
G. Bennett (2006)
Substance P opens cation channels and closes potassium channels in rat locus coeruleus neurons
K. Shen (1992)
Cell-Autonomous Regulation of Mu-Opioid Receptor Recycling by Substance P
Shanna L. Bowman (2015)
Substance P-driven feed-forward inhibitory activity in the mammalian spinal cord
T. Nakatsuka (2005)
Neurokinin 1 Receptor Mediates Membrane Blebbing in HEK293 Cells through a Rho/Rho-associated Coiled-coil Kinase-dependent Mechanism*
J. Meshki (2009)
Substance P and somatostatin inhibit calcium channels in rat sympathetic neurons via different G protein pathwavs
M. S. Shapiro (1993)
Evidence for the involvement of ASIC3 in sensory mechanotransduction in proprioceptors
Shing-Hong Lin (2016)
A low voltage-activated, fully inactivating Ca channel in vertebrate sensory neurones
E. Carbone (1984)
A fragment of substance P with specific central activity: SP(1–7)
J. Stewart (1982)
Substance P and behavior: Opposite effects of N-terminal and C-terminal fragments
M. Hall (1983)
Substance P equals pain
L. Iversen (1998)
NMP-7 inhibits chronic inflammatory and neuropathic pain via block of Cav3.2 T-type calcium channels and activation of CB2 receptors
N. Berger (2014)
Acid-sensing ion channels: dual function proteins for chemo-sensing and mechano-sensing
Yuan-Ren Cheng (2018)
Antinociceptive and Met-enkephalin releasing effects of tachykinins and substance P fragments
J. Naranjo (1986)
Substance P and antinociception
M. Hall (1983)
Substance P equals pain substance ?
L. Iversen (1998)
Immunoregulatory effects of neuropeptides. Stimulation of interleukin-2 production by substance P
P. Rameshwar (1992)
Jevtovic-Todorovic, V. Mechanical and thermal antinociception in rats following systemic administration of mibefradil, a T-type calcium channel blocker
S M Todorovic (2002)
Molecular correlates of the M‐current in cultured rat hippocampal neurons
M. Shah (2002)
Neurokinin 1 receptor and relative abundance of the short and long isoforms in the human brain
L. Caberlotto (2003)
Differential effects of C- and N-terminal substance P metabolites on the release of amino acid neurotransmitters from the spinal cord: potential role in nociception
S. R. Skilling (1990)
An antinociceptive role for substance P in acid-induced chronic muscle pain
C. Lin (2011)
Involvement of Substance P in the Analgesic Effect of Low-Level Laser Therapy in a Mouse Model of Chronic Widespread Muscle Pain.
Der-Sheng Han (2019)
Low-Threshold Calcium Currents in Central Nervous System Neurons
Intravenous Administration of Substance P Attenuates Mechanical Allodynia Following Nerve Injury by Regulating Neuropathic Pain-Related Factors
Eunkyung Chung (2017)
Substance P and analgesia
John M. Stewart (1976)
Sensing acidosis: nociception or sngception?
Jiann-Her Lin (2018)
Modulation of excitatory amino acid responses in rat dorsal horn neurons by tachykinins
M. Randić (1992)
Algesia and local responses induced by neurokinin A and substance P in human skin and temporal muscle
U. Pedersen-Bjergaard (1989)
Pain due to nerve damage: Are inflammatory mediators involved
D. Tracey (2005)
Neurotransmitters and CNS disease. Pain.
Jessell Tm (1982)
Tachykinins Potentiate N‐Methyl‐D‐Aspartate Responses in Acutely Isolated Neurons from the Dorsal Horn
K. Rusin (1993)
Substance P regulates Ih via a NK-1 receptor in vagal sensory neurons of the ferret.
M. Jafri (1998)
Redox-Dependent Modulation of T-Type Ca2+ Channels in Sensory Neurons Contributes to Acute Anti-Nociceptive Effect of Substance P
Dongyang Huang (2016)
This paper is referenced by
Effects of Transcutaneous Auricular Vagus Nerve Stimulation on Peripheral and Central Tumor Necrosis Factor Alpha in Rats with Depression-Chronic Somatic Pain Comorbidity
Xiao Guo (2020)
The Antiallodynic Effect of Nefopam on Vincristine-Induced Neuropathy in Mice
J. Y. Lee (2020)
Ion Channels of Nociception
R. Giniatullin (2020)