Analgesia Mediated by the TRPM8 Cold Receptor in Chronic Neuropathic Pain

@article{Proudfoot2006AnalgesiaMB,
  title={Analgesia Mediated by the TRPM8 Cold Receptor in Chronic Neuropathic Pain},
  author={Clare Proudfoot and Emer M. Garry and David F. Cottrell and Roberta Rosie and Heather A. Anderson and Darren C. Robertson and Susan M. Fleetwood-Walker and Rory Mitchell},
  journal={Current Biology},
  year={2006},
  volume={16},
  pages={1591-1605}
}
BACKGROUND Chronic established pain, especially that following nerve injury, is difficult to treat and represents a largely unmet therapeutic need. New insights are urgently required, and we reasoned that endogenous processes such as cooling-induced analgesia may point the way to novel strategies for intervention. Molecular receptors for cooling have been identified in sensory nerves, and we demonstrate here how activation of one of these, TRPM8, produces profound, mechanistically novel… 
Role of TRPM8 in dorsal root ganglion in nerve injury-induced chronic pain
TLDR
TRPM8 may play different roles in mechanical allodynia, cold and thermal hyperalgesia that develop after nerve injury, and it is a very promising research direction for the development of new therapies for chronic neuroapthic pain.
Transient Receptor Potential Channels in neuropathic pain
TLDR
This review will summarize the current knowledge of the contribution of TRP channels, particularly the thermosensitive TRP, including TRPV1, TRPA1 and TRPM8 channels that play a central role in the sensitization of nociceptive transduction.
The Contribution of TRPM8 and TRPA1 Channels to Cold Allodynia and Neuropathic Pain
TLDR
The results indicate that injured sensory neurons do not develop abnormal cold sensitivity after chronic constriction injury and that alterations in the expression of TRPM8 and TRPA1 are unlikely to contribute directly to the pathogenesis of cold allodynia in this neuropathic pain model.
Differential regulation of TRP channels in a rat model of neuropathic pain
TLDR
The current results link for the first time a re‐expression of TRPML3 with the development of neuropathic pain conditions, and decreased mRNA levels after SNI were seen for TRPM6, TRPM8, TRPV1, TRPA1,TRPC3, TRPC4 and TRPC5.
Targeting TRPM8 for Pain Relief
TLDR
It is suggested that pharmacological modulators of TRPM8 could have potential indications in a variety of conditions, including dry eye disease, airway irritation, teeth hypersensitivity, migraine and neuropathic pain, but additional studies are needed to verify these preliminary observations.
Targeting TRPM 8 for Pain Relief
Transient receptor potential melastatin 8 (TRPM8) is a non-selective cation channel activated by cold temperature and cooling agents. TRPM8 is expressed in peripheral cold thermoreceptors and plays a
TRPM8 Mechanism of Cold Allodynia after Chronic Nerve Injury
TLDR
Together, the gain of TRPM8-mediated cold sensitivity on nociceptive afferent neurons provides a mechanism of cold allodynia.
Targeting TRP channels for pain relief.
TLDR
The promise and challenges of developing TRP channel antagonists as a new generation of pain therapeutics are discussed.
Activation of TRPM8 cold receptor triggers allodynia-like behavior in spinally injured rats
TLDR
Assessment of the role of TRP channels in mediating cold allodynia in rats after ischemic spinal cord injury showed that activation of the TRPM8 channel by menthol or icilin triggers allodynian in spinally injured rats and increases, rather than decreases, mechanical allodyna.
TRPM8 as a Target for Analgesia
Abstract Transient receptor potential melastatin 8 (TRPM8) is a cation channel expressed in a small subpopulation of sensory neurons, which detect innocuous cooling and mostly lack characteristics of
...
1
2
3
4
5
...

References

SHOWING 1-10 OF 67 REFERENCES
TRPA1 induced in sensory neurons contributes to cold hyperalgesia after inflammation and nerve injury.
TLDR
It is demonstrated that an NGF-induced TRPA1 increase in sensory neurons via p38 activation is necessary for cold hyperalgesia, which might provide a fruitful strategy for treating cold hyperAlgesia caused by inflammation and nerve damage.
Inhibition of neuropathic pain by decreased expression of the tetrodotoxin-resistant sodium channel, NaV1.8
TLDR
It is shown that intrathecal administration of specific antisense oligodeoxynucleotides (ODN) to the peripheral tetrodotoxin (TTX)‐resistant sodium channel, NaV1.8, resulted in a time‐dependent uptake of the ODN by dorsal root ganglion (DRG) neurons, and a selective ‘knock‐down’ of the expression of NaV 1.8 which reversed neuropathic pain induced by spinal nerve injury.
Antisense knock down of TRPA1, but not TRPM8, alleviates cold hyperalgesia after spinal nerve ligation in rats
TLDR
The data suggest that increased TRPA1 in uninjured primary afferent neurons may contribute to the exaggerated response to cold observed in the neuropathic pain model.
Focal Lysolecithin-Induced Demyelination of Peripheral Afferents Results in Neuropathic Pain Behavior That Is Attenuated by Cannabinoids
TLDR
This is the first time that demyelination of afferent A-fibers has been shown to specifically induce neuropathic pain and indicates that axonal damage is not a prerequisite for development of the pain state.
TRPA1 Mediates the Inflammatory Actions of Environmental Irritants and Proalgesic Agents
TLDR
Using TRPA1-deficient mice, it is shown that this channel is the sole target through which mustard oil and garlic activate primary afferent nociceptors to produce inflammatory pain.
Topical menthol--a human model for cold pain by activation and sensitization of C nociceptors.
Although cold hyperalgesia is a frequent symptom in patients with neuropathic pain, it is poorly understood. We investigated the mechanisms of cold pain by studying the effect of menthol on pain,
Neuropathic Sensitization of Behavioral Reflexes and Spinal NMDA Receptor/CaM Kinase II Interactions Are Disrupted in PSD-95 Mutant Mice
TLDR
It is shown that PSD-95 plays a key role in neuropathic reflex sensitization, and disruption of CaM kinase II docking to the NMDA receptor and activation may be responsible for the lack of neuropathic behavioral Reflex sensitization in PSd-95 mutant mice.
Impaired nociception and pain sensation in mice lacking the capsaicin receptor.
TLDR
Sensory neurons from mice lacking VR1 are severely deficient in their responses to each of these noxious stimuli and are impaired in the detection of painful heat, and showed little thermal hypersensitivity in the setting of inflammation.
How cold is it? TRPM8 and TRPA1 in the molecular logic of cold sensation
  • D. McKemy
  • Chemistry, Medicine
    Molecular pain
  • 2005
TLDR
The current understanding of these cold thermoreceptors is summarized, as well as the current controversy regarding TRPA1 and cold signaling is addressed.
TRPA1 Contributes to Cold, Mechanical, and Chemical Nociception but Is Not Essential for Hair-Cell Transduction
TLDR
TRPA1 is apparently not essential for hair-cell transduction but contributes to the transduction of mechanical, cold, and chemical stimuli in nociceptor sensory neurons.
...
1
2
3
4
5
...