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Pain from anticancer drugs-induced neuropathies is difficult to treat and can significantly alter the patient's quality of life. These neuropathies are considered relatively resistant to conventional analgesic drugs (opioids). Opioids are also P-glycoprotein substrates and it has been demonstrated that the P-glycoprotein is linked to the integrity of blood-brain barrier protecting the nervous system. Previous works presented an increase of P-glycoprotein in vincristine- and cisplatin-induced neuropathy which could potentially decrease opioid efficiency. To test this hypothesis, the efflux inhibition of P-glycoprotein and the antinociceptive effect of morphine were assessed in normal and cisplatin-induced neuropathic rats after the administration of the P-glycoprotein inhibitor (R101933). R101933 (20 mg/kg) inhibited significantly the efflux transporter under the condition of the study and had no analgesic effect. Nociceptive thresholds were measured by the paw pressure test. R101933 (20 mg/kg) enhanced antinociceptive activity of morphine (0.5 mg/kg) to a maximum of +58% and +35%, respectively compared with control animals and animals treated by morphine alone (0.5 mg/kg). R101933 increased morphine (2 mg/kg) antinociceptive activity to a maximum of +105% compared with control animals and to a maximum of +41% compared with morphine alone (2 mg/kg). This study demonstrated that cisplatin-induced neuropathy may present a particular pathophysiology with a multidrug resistance, of the central nervous system, to analgesics. This resistance can be blocked by a P-glycoprotein inhibitor which may enhance analgesia of low doses of morphine.

The possibility that chronicle oral ingestion of fluoride-rich water could modify peripheral pain sensitivity was studied in two strains of adult rats, Sprague-Dawley and Lou/C rats. Sodium fluoride was given orally in water to male Sprague-Dawley (75 and 150 ppm) and Lou rats (150 ppm) for 15 and 27 weeks, respectively. Using classical behavioural evaluation methods of pain symptoms, only slight tendencies to a thermal hyperalgia and a mechanical allodynia were observed in Sprague-Dawley rats.

This work describes the behavioural responses of Sprague-Dawley rats to mechanical or thermal stimuli during and after administration of ten intraperitoneal injections of, alternatively, 1 and 2 mg/kg cisplatin every three days (cumulative dose: 15 mg/kg). Nociceptive signs including mechanical allodynia and hyperalgesia appeared after 3 and 6 cisplatin injections, respectively, and were maintained until 15 days after the last injection. The conservation of a good clinical status and fast appearance of symptoms are favourable criteria for using this animal model to understand the pathophysiological mechanisms implicated in the cisplatin-induced sensory peripheral neuropathy.