Chemotherapy-induced peripheral neuropathy

Quasthoff, Stefan; Hartung, Hans Peter

doi:10.1007/pl00007853

Cited by 837 publications

(606 citation statements)

References 45 publications

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“…Following administration of paclitaxel patients may experience a range of positive sensory symptoms including spontaneous tingling, burning pain, joint and muscle pain (Postma et al, 1995;Quasthoff & Hartung, 2002;Dougherty et al, 2004) that often occurs in the distal extremities in a "glove and stocking" distribution. These symptoms may increase in severity and be accompanied by sensory deficits including numbness, loss of vibratory sensation, decreased deep tendon reflexes and decreased proprioceptive abilities (Rowinsky et al, 1993;Postma et al, 1995).…”

Section: Introductionmentioning

confidence: 99%

An evolving cellular pathology occurs in dorsal root ganglia, peripheral nerve and spinal cord following intravenous administration of paclitaxel in the rat

et al. 2007

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Paclitaxel (Taxol®) is a frontline antineoplastic agent used to treat a variety of solid tumors including breast, ovarian, or lung cancer. The major dose limiting side effect of paclitaxel is a peripheral sensory neuropathy that can last days to a lifetime. To begin to understand the cellular events that contribute to this neuropathy, we examined a marker of cell injury/regeneration (activating transcription factor 3; ATF3), macrophage hyperplasia/hypertrophy; satellite cell hypertrophy in the dorsal root ganglion (DRG) and sciatic nerve as well as astrocyte and microglial activation within the spinal cord at 1, 4, 6 and 10 days following intravenous infusion of therapeutically relevant doses of paclitaxel. At day 1 post-infusion there was an up-regulation of ATF3 in a subpopulation of large and small DRG neurons and this up-regulation was present through day 10. In contrast, hypertrophy of DRG satellite cells, hypertrophy and hyperplasia of CD68+ macrophages in the DRG and sciatic nerve, ATF3 expression in S100β+ Schwann cells and increased expression of the microglial marker (CD11b) and the astrocyte marker glial fibrillary acidic protein in the spinal cord were not observed until day 6 post infusion. The present results demonstrate that using the time points and markers examined, DRG neurons show the first sign of injury which is followed days later by other neuropathological changes in the DRG, peripheral nerve and dorsal horn of the spinal cord. Understanding the cellular changes that generate and maintain this neuropathy may allow the development of mechanism-based therapies to attenuate or block this frequently painful and debilitating condition.

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Section: Introductionmentioning

confidence: 99%

An evolving cellular pathology occurs in dorsal root ganglia, peripheral nerve and spinal cord following intravenous administration of paclitaxel in the rat

et al. 2007

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“…Neurotoxicity, especially against the somatic and autonomic peripheral nervous system, is the most commonly reported systemic complication (5). Neurotoxicity manifests mainly as peripheral neuropathy with predominant sensory findings.…”

Section: Introductionmentioning

confidence: 99%

Vincristine delays gastric emptying and gastrointestinal transit of liquid in awake rats

Júnior

Teles

Castro

et al. 2009

Braz J Med Biol Res

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We evaluated the effects of vincristine on the gastrointestinal (GI) motility of awake rats and correlated them with the course of vincristine-induced peripheral neuropathy. Vincristine or saline was injected into the tail vein of male Wistar rats (180-250 g) on alternate days: 50 μg/kg (5 doses, N = 10), 100 μg/kg (2, 3, 4 and 5 doses, N = 49) or 150 μg/kg (1, 2, or 5 doses, N = 37). Weight and stool output were measured daily for each animal. One day after completing the vincristine treatment, the animals were fasted for 24 h, gavage-fed with a test meal and sacrificed 10 min later to measure gastric emptying (GE), GI transit and colon weight. Sensory peripheral neuropathy was evaluated by hot plate testing. Chronic vincristine treatments with total cumulative doses of at least 250 μg/kg significantly decreased GE by 31-59% and GI transit by 55-93%. The effect of 5 doses of vincristine (150 μg/kg) on GE did not persist for more than 1 week. Colon weight increased after 2 and 5 doses of vincristine (150 μg/kg). Fecal output decreased up to 48 h after the fifth dose of vincristine (150 μg/kg). Vincristine decreased the heat pain threshold 1 day after 5 doses of 50-100 μg/kg or after 3-5 doses of 150 μg/kg. This effect lasted for at least 2 weeks after the fifth dose. Chronic intravenous vincristine treatment delayed GE and GI transit of liquid. This effect correlated with the peak increase in colon weight but not with the pain threshold changes.

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“…[33][34][35] Microtubule-targeting agents (e.g., paclitaxel, vincristine) display axonal toxicity, with the longest axons being the first affected. 36 For paclitaxel, studies in animal models using high doses initially supported the hypothesis that the drug's neurotoxicity arises from disruption of microtubules and impairment of axonal transport, but numerous reports now refute this idea. [37][38][39][40] Indeed, low doses of paclitaxel caused allodynia and hyperalgesia in rats without inducing degeneration of myelinated and unmyelinated axons in the sciatic nerve and roots.…”

Section: Chemotherapy-induced Peripheral Neuropathymentioning

confidence: 99%

Targeting Neuroprotection as an Alternative Approach to Preventing and Treating Neuropathic Pain

Bordet

Pruss

2009

Neurotherapeutics

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Summary:Neuropathic pain syndromes arise from dysfunction of the nerve itself, through traumatic or nontraumatic injury. Unlike acute pain syndromes, the pain is long-lasting and does not respond to common analgesic therapies. Drugs that disrupt nerve conduction and transmission or central sensitization, currently the only effective treatments, are only modestly effective for a portion of the patients suffering from neuropathic pain and come with the cost of serious adverse effects. Neurodegeneration, as a reaction to nerve trauma or chronic metabolic or chemical intoxication, appears to be an underlying cause of neuropathic pain. Identifying mechanisms of neurodegeneration and designing neuroprotective therapies is an ambitious goal toward treating or even preventing the development of these disabling disorders.

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Chemotherapy-induced peripheral neuropathy

Cited by 837 publications

References 45 publications

An evolving cellular pathology occurs in dorsal root ganglia, peripheral nerve and spinal cord following intravenous administration of paclitaxel in the rat

An evolving cellular pathology occurs in dorsal root ganglia, peripheral nerve and spinal cord following intravenous administration of paclitaxel in the rat

Vincristine delays gastric emptying and gastrointestinal transit of liquid in awake rats

Targeting Neuroprotection as an Alternative Approach to Preventing and Treating Neuropathic Pain

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