Different peripheral mechanisms mediate enhanced nociception in metabolic/toxic and traumatic painful peripheral neuropathies in the rat
Section snippets
Animals
Experiments were performed on 220–260-g male Sprague–Dawley rats (Bantin and Kingman, Fremont CA, USA). Rats were housed in groups of two under a 12-h light–dark cycle. Food and water were available ad libitum. Experiments were carried out in accordance with NIH regulations for animal care and with the approval of the Institutional Animal Care and Use Committee of the University of California, San Francisco.
Vincristine-induced (chemotherapy) painful neuropathy
Vincristine sulfate (Sigma, St. Louis, MO, USA) was dissolved in saline to a stock
Vincristine-induced hyperalgesia and allodynia
Vincristine treatment (n=16) resulted in a significant decrease in nociceptive threshold 72–168 h after the last vincristine administration, compared to normal saline treatment (n=6) (Fig. 1A; P<0.01). Evaluation of response to von Frey hair testing (10 mN through 209 mN) demonstrated a significant increase in percent frequency of paw withdrawals (Fig. 1B; both n=12; P<0.01, test done 96 h after the last vincristine administration).
Streptozotocin-induced (diabetic) hyperalgesia and allodynia
STZ treatment resulted in a significant decrease in nociceptive
Discussion
We report on a comparison of peripheral mechanisms underlying four important experimental models, of neuropathic pain states established in the rat. Although all four models manifested a similar degree of persistent mechanical hyperalgesia and allodynia, there was a significant difference in the underlying second messengers in the peripheral terminals of primary afferent nociceptors contributing to mechanical hyperalgesia. In the models of diabetic and vincristine-induced painful neuropathy the
Acknowledgements
Funded by NIH grants NS21445, NS42546 and DE08973.
References (49)
- et al.
Mechanical hyperalgesia in streptozotocin-diabetic rats
Neuroscience
(1993) - et al.
Rapid onset pain induced by intravenous streptozotocin in the rat
J. Pain
(2001) - et al.
Vincristine hyperalgesia in the rat: a model of painful vincristine neuropathy in humans
Neuroscience
(1996) Dose-response relationship of opioids in nociceptive and neuropathic postoperative pain
Pain
(1998)- et al.
A peripheral mononeuropathy in rat that produces disorders of pain sensation like those seen in man
Pain
(1988) - et al.
Quantitative assessment of tactile allodynia in the rat paw
J. Neurosci. Methods
(1994) - et al.
Streptozocin-induced diabetic rats: behavioural evidence for a model of chronic pain
Pain
(1993) - et al.
The safety and efficacy of a single dose (500 mg or 1 g) of intravenous magnesium sulfate in neuropathic pain poorly responsive to strong opioid analgesics in patients with cancer
J. Pain Symptom Manage.
(2000) - et al.
Postherpetic neuralgia: irritable nociceptors and deafferentation
Neurobiol. Dis.
(1998) - et al.
Critical evaluation of the streptozotocin model of painful diabetic neuropathy in the rat
Pain
(1999)
Alpha-phenyl-tert-butylnitrone (PBN) inhibits NFkappaB activation offering protection against chemically induced diabetes
Free Radic. Biol. Med.
Glutamate participates in the peripheral modulation of thermal hyperalgesia in rats
Eur. J. Pharmacol.
A novel nociceptor signaling pathway revealed in protein kinase C mutant mice
Neuron
Involvement of the sympathetic postganglionic neuron in capsaicin-induced secondary hyperalgesia in the rat
Neuroscience
A transient osmotic permeabilization method for the introduction of impermeant molecules into functional brain membrane vesicles
J. Neurosci. Methods
Effect of lamotrigine in the acute and chronic hyperalgesia induced by PGE2 and in the chronic hyperalgesia in rats with streptozotocin-induced diabetes
Pain
A novel behavioral model of neuropathic pain disorders produced by partial sciatic nerve injury in rats
Pain
Neuropathic pain: aetiology, symptoms, mechanisms, and management
Lancet
Evaluation of the efficacy of thiamine and pyridoxine in the treatment of symptomatic diabetic peripheral neuropathy
East Afr. Med. J.
Protein kinase C inhibitors decrease hyperalgesia and C-fiber hyperexcitability in the streptozotocin-diabetic rat
J. Neurophysiol.
Opioid and adenosine peripheral antinociception are subject to tolerance and withdrawal
J. Neurosci.
Multiple second messenger systems act sequentially to mediate rolipram-induced prolongation of prostaglandin E2-induced mechanical hyperalgesia in the rat
Neuroscience
Dissociation of tolerance and dependence for opioid peripheral antinociception in rats
J. Neurosci.
Role of protein kinase A in the maintenance of inflammatory pain
J. Neurosci.
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