Beyond Neuropathic Pain

Yan, Peter; Butler, Paul; Kurowski, Donna; Perloff, Michael D.

doi:10.1097/ajp.0000000000000014

Cited by 40 publications

(15 citation statements)

References 86 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Gabapentin is an anticonvulsant drug, commonly used to treat different kinds of pain [200]. When tested on CA1 pyramidal cells, Gabapentin increased I h amplitude in a concentration dependent way, by increasing conductance without affecting activation properties, with a cAMP independent mechanism [201].…”

Section: Substances That Have Been Shown To Modulate Hcn Channel Actimentioning

confidence: 99%

HCN Channels Modulators: The Need for Selectivity

Romanelli

Sartiani²,

Masi³

et al. 2016

CTMC

View full text Add to dashboard Cite

Hyperpolarization-activated, cyclic nucleotide-gated (HCN) channels, the molecular correlate of the hyperpolarization-activated current (I f /I h ), are membrane proteins which play an important role in several physiological processes and various pathological conditions. In the Sino Atrial Node (SAN) HCN4 is the target of ivabradine, a bradycardic agent that is, at the moment, the only drug which specifically blocks I f . Nevertheless, several other pharmacological agents have been shown to modulate HCN channels, a property that may contribute to their therapeutic activity and/or to their side effects.HCN channels are considered potential targets for developing drugs to treat several important pathologies, but a major issue in this field is the discovery of isoform-selective compounds, owing to the wide distribution of these proteins into the central and peripheral nervous systems, heart and other peripheral tissues. This survey is focused on the compounds that have been shown, or have been designed, to interact with HCN channels and on their binding sites, with the aim to summarize current knowledge and possibly to unveil useful information to design new potent and selective modulators.

show abstract

Section: Substances That Have Been Shown To Modulate Hcn Channel Actimentioning

confidence: 99%

HCN Channels Modulators: The Need for Selectivity

Romanelli

Sartiani²,

Masi³

et al. 2016

CTMC

View full text Add to dashboard Cite

show abstract

“…While the reason for this is likely multifactorial, perhaps the earlier discontinuation of neuromodulator medication by male patients was a contributing factor. Further investigation is warranted, as the efficacy of perioperative neuromodulator use remains unclear 41 - 43 .…”

Section: Discussionmentioning

confidence: 99%

Targeted Muscle Reinnervation at the Time of Major Limb Amputation in Traumatic Amputees

et al. 2020

View full text Add to dashboard Cite

Background: Orthopaedic trauma etiologies are a common cause for amputation. Targeted muscle reinnervation (TMR) is a technique aimed at reducing or preventing pain and improving function. The purpose of this study was to examine postoperative phantom limb pain and residual limb pain following TMR in orthopaedic trauma amputees. In addition, postoperative rates of opioid and neuromodulator medication use were evaluated. Methods: Twenty-five patients (60% male) prospectively enrolled in a single-institution study and underwent TMR at the time of major limb amputation (48% nonmilitary trauma, 32% infection secondary to previous nonmilitary trauma, and 20% other, also secondary to trauma). Phantom limb pain and residual limb pain scores, pain temporality, prosthetic use, and unemployment status were assessed at the time of follow-up. The use of opioid and neuromodulator medications both preoperatively and postoperatively was also examined. Results: At a mean follow-up of 14.1 months, phantom limb pain and residual limb pain scores were low, with 92% of the patients reporting no pain or brief intermittent pain only. Pain scores were higher overall for male patients compared with female patients (p < 0.05) except for 1 subscore, and higher in patients who underwent amputation for infection (odds ratio, 9.75; p = 0.01). Sixteen percent of the patients reported opioid medication use at the time of the latest documented follow-up. Fifty percent of the patients who were taking opioids preoperatively discontinued use postoperatively, while 100% of the patients who were not taking opioids preoperatively discontinued postoperative use. None of the patients who were taking neuromodulator medication preoperatively discontinued use postoperatively (0 of 5). The median time to neuromodulator medication discontinuation was 14.6 months, with female patients taking longer than male patients (23 compared with 7 months; p = 0.02). At the time of the latest follow-up, the rate of reported prosthetic use was 85% for lower-extremity and 40% for upper-extremity amputees, with a rate of unemployment due to disability of 36%. Conclusions: The use of TMR in orthopaedic trauma amputees was associated with low overall pain scores at 2-year follow-up, decreased overall opioid and neuromodulator medication use, and an overall high rate of daily prosthetic use. Level of Evidence: Therapeutic Level IV . See Instructions for Authors for a complete description of levels of evidence.

show abstract

“…Eu1.6 exhibits significant analgesic activity in neuropathic pain (PNL and CCI) models at a low dose (5.0~25.0 μg/kg) and was higher than Vc1.1 and the combination of morphine (5 mg/kg, sc) and gabapentin (100 mg/kg, i.g.). The latter combination is effective in current neuropathic pain therapy 40 , 41 . Similar results were observed in the CCI model.…”

Section: Discussionmentioning

confidence: 99%

A novel α-conopeptide Eu1.6 inhibits N-type (CaV2.2) calcium channels and exhibits potent analgesic activity

Liu¹,

Bartels

Sadeghi

et al. 2018

Sci Rep

View full text Add to dashboard Cite

We here describe a novel α-conopeptide, Eu1.6 from Conus eburneus, which exhibits strong anti-nociceptive activity by an unexpected mechanism of action. Unlike other α-conopeptides that largely target nicotinic acetylcholine receptors (nAChRs), Eu1.6 displayed only weak inhibitory activity at the α3β4 and α7 nAChR subtypes and TTX-resistant sodium channels, and no activity at TTX-sensitive sodium channels in rat dorsal root ganglion (DRG) neurons, or opiate receptors, VR1, KCNQ1, L- and T-type calcium channels expressed in HEK293 cells. However, Eu1.6 inhibited high voltage-activated N-type calcium channel currents in isolated mouse DRG neurons which was independent of GABAB receptor activation. In HEK293 cells expressing CaV2.2 channels alone, Eu1.6 reversibly inhibited depolarization-activated Ba2+ currents in a voltage- and state-dependent manner. Inhibition of CaV2.2 by Eu1.6 was concentration-dependent (IC50 ~1 nM). Significantly, systemic administration of Eu1.6 at doses of 2.5–5.0 μg/kg exhibited potent analgesic activities in rat partial sciatic nerve injury and chronic constriction injury pain models. Furthermore, Eu1.6 had no significant side-effect on spontaneous locomotor activity, cardiac and respiratory function, and drug dependence in mice. These findings suggest α-conopeptide Eu1.6 is a potent analgesic for the treatment of neuropathic and chronic pain and opens a novel option for future analgesic drug design.

show abstract

Beyond Neuropathic Pain

Cited by 40 publications

References 86 publications

HCN Channels Modulators: The Need for Selectivity

HCN Channels Modulators: The Need for Selectivity

Targeted Muscle Reinnervation at the Time of Major Limb Amputation in Traumatic Amputees

A novel α-conopeptide Eu1.6 inhibits N-type (CaV2.2) calcium channels and exhibits potent analgesic activity

Contact Info

Product

Resources

About