Dual Diagnosis

Introduction: Paracetamol is one of the most widely used drugs as antipyretic and analgesic for mild to moderate pain. Currently,

paracetamol is the fi rst-line of choice for pain management and antipyresis. Ion channels are involved in many cellular processes;

drugs acting on ion channels have long been used for the treatment of many diseases.

Objective: To evaluate the eff ect of voltage gated ion channel blockers on analgesic activity of Paracetamol.

Material & Methods: Th e central antinociceptive activity was determined by hot plate test and formalin test (Phase I), using male

albino mice. Anti-infl ammatory activity was determined by formalin test (Phase II). Seven groups of mice were used. Group 1:

control group (1% T80); group 2: treated with (200mg/kg) paracetamol; group 3: treated with diff erent ion channel blockers; group 4:

received combined treatment of ion channel blockers and paracetamol; group 5: received standard drugs as Aspirin (200mg/kg) for

formalin test or tramadol (5mg/kg) for hot plate test. Intraperitoneal injection was adopted.

Results: Pain produced by noxious stimuli (heat and formalin) was signifi cantly reduced by acute administration of paracetamol.

Infl ammation pain produced by formalin injection was signifi cantly decreased by acute administration of paracetamol. Nifedipine

has signifi cant decrease in nociceptive pain (hot plate and formalin test, phase I) and infl ammatory pain (formalin test, phase II).

Verapamil did not produce analgesic or anti-infl ammatory eff ects. Phenytoin produced signifi cant decrease in nociceptive pain using

hot plate test and decrease infl ammatory pain in formalin test (Phase II), while phase I is not sensitive for phenytoin. 4-aminopyridine

produces signifi cant decrease in nociceptive and infl ammatory pain. Combined treatment of nifedipine and paracetamol has

antinociceptive and anti-infl ammatory eff ects but less than the additive eff ect. Verapamil administration with paracetamol produces

antinociceptive and anti-infl ammatory activity. Th is eff ect is due to paracetamol only. Administration of combined treatment of

phenytoin and paracetamol has antinociceptive action and anti-infl ammatory eff ect but less than the additive eff ect which may

reach the ceiling.Th e combined treatment of 4-aminopyridine and paracetamol showed antinociceptive action, 4-aminopyridine

potentiates the eff ect of paracetamol; while the anti-infl ammatory action was less than the additive eff ect.

Conclusion: Paracetamol has central analgesic and anti-infl ammatory eff ect. Nifedipine, phenytoin and 4-aminopyridine, each

alone, produce analgesic and anti-infl ammatory action. Verapamil, in the dose used, by its self has neither analgesic nor antiinfl

ammatory eff ect. Paracetamol analgesic action is not aff ected by nifedipine or phenytoin; it may be concluded that the combined

treatment may reach the ceiling eff ect of analgesic action, while analgesic eff ect of paracetamol is potentiated by 4 aminopyridine.

Combined treatment of nifedipine, phenytoin or 4-aminopyridine with paracetamol produce anti-infl ammatory eff ect, which less

than the additive eff ect. Ceiling eff ect of anti-infl ammatory activity may be produced by combined administration of paracetamol and

nifedipine, phenytoin or 4-aminopyridine. Hot plate model is more sensitive to the eff ect of analgesic agent that relieve neuropathic

pain compared to formalin test (phase I).