New investigational drugs for the treatment of neuropathic pain

Sałat, Kinga; Kowalczyk, Paulina; Gryzło, Beata; Jakubowska, Anna; Kulig, Katarzyna

doi:10.1517/13543784.2014.916688

Cited by 36 publications

(15 citation statements)

References 59 publications

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“…Unfortunately, these efforts have, to date, had only limited success in terms of new drug registrations. There have been some successes, particularly in the last few years, with positive phase II trials in pain and related sensory disturbances using anti-NGF, sodium channel blockers, and Angiotensin II receptor and P2X3 receptor antagonists [105][106][107][108][109][110][111][112]. One of the blocks to drug development in this area has been translation from preclinical studies to humans.…”

Section: Discussionmentioning

confidence: 99%

Ultraviolet Radiation on the Skin: A Painful Experience?

Lopes

McMahon

2015

CNS Neurosci Ther

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SummaryExcessive exposure of skin to ultraviolet radiation (UVR) has dramatic clinical effects in humans, and it is a significant public health concern. Discomfort and sensory changes caused by skin sunburn are the main common features experienced by many of us, a phenomena triggered by the combination of long and short wavelengths radiation (UVA and UVB, respectively). Although the biological processes underlying UVR exposure are not fully understood, in the last few years many studies have made significant progress in characterizing sunburn at the cellular and molecular levels, making use of both humans and laboratory animal models. Here we review and reason that UVR can be used as an excellent model of sensitization and inflammation for pain research. UVR, particularly UVB, produces a controllable and sterile inflammation that causes a robust dose‐dependent hypersensitivity with minimal confounding effects. Importantly, we show that UVR animal models precisely recapitulate the sensory, cellular, and molecular changes observed in human skin, giving it great confidence as a translational model. Furthermore, in this article, we give an overview of the pharmacology underlying UVB inflammation, the latest advances in the field, and potential new targets for inflammatory pain.

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Section: Discussionmentioning

confidence: 99%

Ultraviolet Radiation on the Skin: A Painful Experience?

Lopes

McMahon

2015

CNS Neurosci Ther

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“…AT 2 R antagonists may be available for chronic pain management in the future. 56 In addition, the rationale of ACE inhibitors increases the pain sensitivity, because it not only produces inhibition of ACE activity, but also inactivates the opioid peptide [Leu5] enkephalin in the rat, 57 whereas the treatment of ramipril reported to have beneficial effects on glucose-fed induced sensory polyneuropathy in rats via down regulation of pro-nociceptive kinin B 1 receptors. 58 Furthermore, Ang III as well as Ang IV is biologically active and formed from angiotensin II via ACE activity.…”

Section: Discussionmentioning

confidence: 99%

Ameliorative potential of angiotensin-converting enzyme inhibitor (ramipril) on chronic constriction injury of sciatic nerve induced neuropathic pain in mice

Kaur

Muthuraman

Kaur

2014

J Renin Angiotensin Aldosterone Syst

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Introduction: The present study was designed to investigate the effect of ramipril (angiotensin-converting enzyme inhibitor) on the chronic constriction injury of sciatic nerve induced neuropathic pain in mice. Methods: The neuropathic pain was induced by four loose ligations of the right sciatic nerve in mice. The battery of behavioral tests, i.e. plantar, pin prick, tail flick, tail pinch, rota rod tests, were performed to assess the degree of thermal and mechanical hyperalgesia in ipsilateral paw and tail, and motor in-coordination activity respectively. In addition, the biochemical tests, i.e. total protein, thiobarbituric acid reactive substances and reduced glutathione, were also performed in sciatic nerve tissue samples. Results: The administration of ramipril (2 and 4 mg/kg, p.o.) significantly attenuated chronic constriction injury-induced rise in peripheral as well as central pain sensitivity (thermal and mechanical) along with impairment of motor in-coordination activity. Further, it also produces ameliorative effects on chronic constriction injury-induced rise in thiobarbituric acid reactive substances and decrease in glutathione levels when compared with a normal control group. Conclusion: It may be concluded that angiotensin-converting enzyme inhibitor may be a potential new target for the management of neuropathic pain.

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“…Subsequent work led to the development of and clinical approval for Prialt for spinal drug delivery [ 371 ]. Recent efforts to develop a systemically active N-type calcium channel blocker failed to meet efficacy standards in Phase II clinical studies for activity in lumbosacral radiculopathy (NCT01655849), and in post-herpetic neuralgia (NCT017578) (see [ 372 ]).…”

Section: Predictive Successes/failures Of Preclinical Models Of Nocicmentioning

confidence: 99%

The search for novel analgesics: targets and mechanisms

et al. 2015

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The management of the pain state is of great therapeutic relevance to virtually every medical specialty. Failure to manage its expression has deleterious consequence to the well-being of the organism. An understanding of the complex biology of the mechanisms underlying the processing of nociceptive information provides an important pathway towards development of novel and robust therapeutics. Importantly, preclinical models have been of considerable use in determining the linkage between mechanism and the associated behaviorally defined pain state. This review seeks to provide an overview of current thinking targeting pain biology, the use of preclinical models and the development of novel pain therapeutics. Issues pertinent to the strengths and weaknesses of current development strategies for analgesics are considered.

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New investigational drugs for the treatment of neuropathic pain

Cited by 36 publications

References 59 publications

Ultraviolet Radiation on the Skin: A Painful Experience?

Ultraviolet Radiation on the Skin: A Painful Experience?

Ameliorative potential of angiotensin-converting enzyme inhibitor (ramipril) on chronic constriction injury of sciatic nerve induced neuropathic pain in mice

The search for novel analgesics: targets and mechanisms

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