A Rat Pain Model of Vincristine-Induced Neuropathy

Higuera, Emiliano S.; Luo, Z. David

doi:10.1385/1-59259-770-x:091

Cited by 9 publications

(9 citation statements)

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“…Experimental nerve injuries to model clinical neuropathies can also be achieved by treatment with various chemical agents. For example, cancer chemotherapies, such as vincristine and paclitaxel, produce neuropathic pain in humans, and these compounds also produce neuropathy-associated allodynia and hyperalgesia in rodents (Higuera and Luo, 2004). Diabetic neuropathies can be modeled by the cytotoxic destruction of pancreatic ␤-cells through the administration of streptozotocin (Fox et al, 1999;Calcutt, 2004).…”

Section: Toward More Clinically Relevant Pain Statesmentioning

confidence: 99%

Preclinical Assessment of Candidate Analgesic Drugs: Recent Advances and Future Challenges

Negus

Vanderah²,

Brandt

et al. 2006

J Pharmacol Exp Ther

219

201

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In analgesic drug development, preclinical procedures are widely used to assess drug effects on pain-related behaviors. These procedures share two principal components: 1) a manipulation intended to produce a pain-like state in the experimental subject and 2) measurement of behaviors presumably indicative of that pain state. Drugs can then be evaluated for their ability to attenuate pain-related behaviors. In the simplest procedures, the pain state is produced by delivery of an acute noxious stimulus (e.g., a warm thermal stimulus), and the primary dependent measures focus on withdrawal responses or other nocifensive behaviors that increase in rate, frequency, or intensity in response to the noxious stimulus. This approach has been refined in two ways. First, new methods have been developed to induce more clinically relevant pain states. In particular, pain requiring clinical intervention is often associated with inflammation or neuropathy, and novel procedures have emerged to model these conditions and their ability to produce hypersensitive pain states, such as allodynia and hyperalgesia. Second, studies are incorporating a broader array of painrelated behaviors as dependent measures. For example, pain not only stimulates nocifensive behaviors but also suppresses many adaptive behaviors, such as feeding or locomotion. Measures of pain-suppressed behaviors can provide new insights into the behavioral consequences of pain and the effects of candidate analgesics. In addition, functional magnetic resonance imaging has emerged as a noninvasive tool for investigating changes in neural activity associated with pain and analgesia. Integration of these complementary approaches may improve the predictive validity of analgesic drug development.

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Section: Toward More Clinically Relevant Pain Statesmentioning

confidence: 99%

Preclinical Assessment of Candidate Analgesic Drugs: Recent Advances and Future Challenges

Negus

Vanderah²,

Brandt

et al. 2006

J Pharmacol Exp Ther

219

201

View full text Add to dashboard Cite

show abstract

“…The study of neuropathic pain requires appropriate animal models that reproduce most of the chronic pain states observed in humans. Neuropathic pain can be modelled in animals using metabolic models (such as diabetic neuropathic pain) (Courteix et al, 1993), pharmacological models (such as specific anti-cancerous treatments) (Higuera and Luo, 2004;Ling et al, 2007), or traumatic models (Bennet and Xie, 1988;Seltzer et al, 1990;Kim and Chung, 1992). In 1996, Mosconi and Kruger described a model of peripheral neuropathic pain in which short cuffs of polyethylene tubing were placed around the main branch of sciatic nerve in rats.…”

Section: Introductionmentioning

confidence: 99%

Sciatic nerve cuffing in mice: A model of sustained neuropathic pain

Benbouzid

Pallage

Rajalu

et al. 2008

European Journal of Pain

125

128

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Because of its severity, chronicity, resistance to usual therapy and its consequences on quality of life, neuropathic pain represents a real clinical challenge. Fundamental research on this pathology uses metabolic, pharmacological or traumatic models in rodents that reproduce the characteristic human pain symptoms. In 1996, Mosconi and Kruger morphologically described a model of peripheral neuropathy in which a cuff of polyethylene tubing was placed around the sciatic nerve in rats. In the present study, we evaluated the behavioral consequences of this neuropathic pain model in C57Bl/6J mice which is the main genetic background used for studies in transgenic mice. A short cuff of polyethylene tubing was unilaterally placed around the main branch of the sciatic nerve. It induced an ipsilateral heat thermal hyperalgesia lasting around 3 weeks, and a sustained ipsilateral mechanical allodynia lasting at least 2 months. We showed that this neuropathic pain model is insensitive to ketoprofen, a non-steroidal anti-inflammatory drug. Morphine treatment acutely suppressed the mechanical allodynia, but tolerance to this effect rapidly developed. The analysis of video recordings revealed that most aspects of spontaneous behavior remained unaffected on the long term, excepted for a decrease in the time spent at social interaction for the neuropathic mice. Using the elevated plus-maze and the marble-burying test, we also showed that neuropathic mice develop an anxiety phenotype. Our data indicate that sciatic nerve cuffing in mice is a pertinent model for the study of nociceptive and emotional consequences of sustained neuropathic pain.

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“…VIN lowers the pain threshold in rats, which confirms its use as a model substance to induce NP [46][47][48]. This drug is used during chemotherapy regimens in cancer patients.…”

Section: Research Wojciech Leppertmentioning

confidence: 52%

Analgesic and Anti–Inflammatory Effects of Oxycodone with Adjuvant Drugs in an Experimental Study of Nociceptive and Neuropathic Pain

Leppert¹,

Szulc²,

Kaczmarek³

et al. 2018

Neuropsychiatry

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Objective: Opioids are often combined with adjuvants to treat symptoms that accompany pain and with adjuvant analgesics to treat neuropathic pain. Herein, we aim to investigate the analgesic and anti-inflammatory effects of oxycodone and selected adjuvants in rats.Methods: Analgesic and anti-inflammatory effects of oxycodone were assessed after single subcutaneous (SC) (0.56 mg/kg) injections in rats, with the following drugs: midazolam (0.3 mg/kg), haloperidol (0.45 mg/kg), ketamine (0.3 mg/kg), hyoscine butylbromide (1.7 mg/kg), levomepromazine (0.35 mg/kg), and metoclopramide (1.0 mg/kg). Analgesia was assessed by the tail flick test. Anti-inflammatory activity was evaluated using a plethysmometer after carrageenan-induced edema. For neuropathic pain, analgesia was explored using the tail flick and von Frey tests. Neuropathic pain was induced by vincristine (0.1 mg/kg, i.p.) in male Wistar rats.Results: All tested combinations of oxycodone with particular adjuvants showed increased analgesia in comparison to oxycodone alone. Compared to oxycodone alone, combinations with midazolam, haloperidol, hyoscine butylbromide, and levomepromazine prolonged analgesia. Anti-inflammatory activities were observed after coadministration of oxycodone paired with haloperidol and ketamine, which is a new aspect of the pharmacological profile of oxycodone. In the neuropathic pain model, vincristine lowered pain threshold in rats and inhibited growth of normal rat body weight. Oxycodone in combination with adjuvant analgesics showed more potent analgesia than oxycodone alone, especially in the tail-flick test. In most cases, the maximum effects were observed for 15-30 min since combined SC administration.Conclusions: Analgesic and anti-inflammatory effects were observed in oxycodone combined with selected adjuvants in rats; although the mechanism of these interactions is not yet well understood. Further studies should test these combinations after chronic administration and assess the benefits and risks associated with the use of the tested combinations in humans.

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A Rat Pain Model of Vincristine-Induced Neuropathy

Cited by 9 publications

References 0 publications

Preclinical Assessment of Candidate Analgesic Drugs: Recent Advances and Future Challenges

Preclinical Assessment of Candidate Analgesic Drugs: Recent Advances and Future Challenges

Sciatic nerve cuffing in mice: A model of sustained neuropathic pain

Analgesic and Anti–Inflammatory Effects of Oxycodone with Adjuvant Drugs in an Experimental Study of Nociceptive and Neuropathic Pain

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