DOI: http://dx.doi.org/10.18203/2320-6012.ijrms20180427

Antinociceptive evaluation of conventional anticonvulsant with conventional analgesics on pain model of albino rats and mice

Ruchika Agarwal, Saurabh Kansal

Abstract


Background: Pain is one of the most common presentations of any disorder and needs immediate and appropriate attention of the treating physician. As pain syndrome involves a variety of etiopathogenesis and temporal domains, management of pain as such requires consideration of many factors that may dictate appropriate therapeutic management. Carabmazepine is an established drug for trigeminal neuralgia while Gabapentin has been tried in postoperative pain but its effectiveness per se and when compared to conventional analgesics needs to be evaluated.

Methods: The present study was planned to study the analgesic effects of Gabapentin in various pain models like writhing and formalin test and to compare it with conventional analgesics like Diclofenac sodium and Tramadol in various acute pain models.

Results: This study has been carried out in department of Pharmacology, HIMS, Dehradun, for evaluation of Gabapentin for its antinociceptive effect in rats and mice. In the writhing test, a reduction in number of writhes, though insignificant, was found in the Gabapentin pre-treatment group. However, in the first phase of Formalin test which is characterized by licking and biting, Gabapentin produced no significant effect in comparison to control values. In the second phase of leg raising (LR), all three drugs, i.e. Gabapentin and the two positive controls i.e. diclofenac and tramadol produced significant decrease (p< 0.05) in episodes when compared to the control group.

Conclusions: Hence the result conclude that Gabapentin could be an effective analgesic drug in visceral and chronic pain in humans but not in acute pain as first phase of formalin test is model of acute and second phase denote chronic pain while writhing test is a model of visceral pain.


Keywords


Analgesics, Diclofenac, Gabapentin, Tramadol

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References


References

.

Maizes M, Mccarberg B. Antidepressant and antiepileptic drugs for chronic noncancer pain. Am Fam Physician 2005; 71: 483-90.

Merskey H, Albe-Fessard DG, Bonica JJ, Carmon A, Dubner R, Kerr FWL et al. Pain terms a list with definitions and notes on usage. Pain 1979; 6: 249-52.

Arrie K, Jones SC. Efficacy of duloxitine, a potent and balanced serotonergic and noradrenergic reuptake inhibitor, in inflammatory and acute pain models in rodents. J Pharmacol Exp Ther 2005; 313: 726-32

Pandi PV, Nagappa AN. Effect of acute and chronic treatment of losartan potassium on tailflick response in mice. Ind J Pharmacol 2006; 38: 281-2.

Vogel HG, Vogel WGH, editors, Drug discovery and evaluation-pharmacological assays. 2nd ed. New York: Verlog Springer publication;1996.

Christian D, Miranda HF, Raquel P, Mases A, Eulalia P. Synergistic interaction between dexamethasone and tramadol in a murine model of acute visceral pain. Fundamental Clin Pharmacol 2007; 21: 515-20.

Miranda HF, Pelissier T, Pinardi G. Involvement of adrenergic, serotonergic and opioid mechanisms in tramadol –induced antinociception in mice. Analgesia 1999; 4: 1-7.

Hernandez GC, Soto VG, Ortiz MI. Pinacidil increases diclofenac antinociception in the formalin test. Proc West Pharmacol Soc 2005; 48: 55-8.

Vogel HG, Vogel WGH, editors, Drug discovery and evaluation-pharmacological assays. 2nd ed. New York: Verlog Springer publication;1996.

Pooja S, Agrawal RP, Nyati P, Savita V, Phadnis P. Analgesic activity of piper nigrum extract per se and its interaction with diclofenac sodium and pentazocine in albino mice. Internet Jour Pharmacol 2007; 5: 181-9.

Assi D, Azim A, Rahman A, Mahran S. Analgesic effects of tramadol-diclofenac combination and their interaction with sycostimulant drugs in mice and rats. Eur J Pharmacol 1996;312:132-8.

Raffa RB, Friderichs E, Reimann W, Shank RP, Codd EE, Vaught JL. Opioid and nonopioid components independently contribute to the mechanism of action of tramadol, an atypical opioid analgesic. J Pharmacol Exp Ther 1992; 260: 275-85.

Cheng JK, Lai YJ, Chen CC, Cheng CR, Chiou LC. Magnesium chloride and ruthenium red attenuate the antiallodynic effect of intrathecal gabapentin in arat model of postoperative pain. Anesthesiology 2003; 98: 1472-9.

Heughan CE, Sawynok J. The interaction between gabapentin and amitryptyline in the rat formalin test after systemic administration. Anesth Analg 2002; 94: 975-80.

Field MJ, Hughes J, Singh L. Further evidence for the role of the alpha2 delta subunit of voltage dependent calcium channels in models of neuropathic pain. Br J Pharmacol 2000; 13: 282-6.

Dickenson D, Sullivan AF. Peripheral origins and central modulation of subcutaneous formalin induced activity of rat dorsal horn neurons. Neurosci Lett 1987; 83: 207-11.

Shannon HE, Eberle EL, Peters SC. Comparison of the effects of anticonvulsant drugs with diverse mechanisms of action in the formalin test in rats. Neuropharmacology 2005;48:1012-20.

Carlton SM, Zhou S. Attenuation of formalin induced nociceptive behaviors following local peripheral injection of gabapentin. Pain 1998; 76: 201-7.

Feng Y, Cui M, Willis WD. Gabapentin markedly reduces acetic acid induced visceral nociception. Anesthesiology 2003; 98: 131-9.

Blackburn MG, Ibsen N, Erichsen HK. A comparison of the antinociceptive effects of voltage activated Na+ channel blockers in the formalin test. Eur J Pharmacol 2002; 445: 231-8.

References

.

Maizes M, Mccarberg B. Antidepressant and antiepileptic drugs for chronic noncancer pain. Am Fam Physician 2005; 71: 483-90.

Merskey H, Albe-Fessard DG, Bonica JJ, Carmon A, Dubner R, Kerr FWL et al. Pain terms a list with definitions and notes on usage. Pain 1979; 6: 249-52.

Arrie K, Jones SC. Efficacy of duloxitine, a potent and balanced serotonergic and noradrenergic reuptake inhibitor, in inflammatory and acute pain models in rodents. J Pharmacol Exp Ther 2005; 313: 726-32

Pandi PV, Nagappa AN. Effect of acute and chronic treatment of losartan potassium on tailflick response in mice. Ind J Pharmacol 2006; 38: 281-2.

Vogel HG, Vogel WGH, editors, Drug discovery and evaluation-pharmacological assays. 2nd ed. New York: Verlog Springer publication;1996.

Christian D, Miranda HF, Raquel P, Mases A, Eulalia P. Synergistic interaction between dexamethasone and tramadol in a murine model of acute visceral pain. Fundamental Clin Pharmacol 2007; 21: 515-20.

Miranda HF, Pelissier T, Pinardi G. Involvement of adrenergic, serotonergic and opioid mechanisms in tramadol –induced antinociception in mice. Analgesia 1999; 4: 1-7.

Hernandez GC, Soto VG, Ortiz MI. Pinacidil increases diclofenac antinociception in the formalin test. Proc West Pharmacol Soc 2005; 48: 55-8.

Vogel HG, Vogel WGH, editors, Drug discovery and evaluation-pharmacological assays. 2nd ed. New York: Verlog Springer publication;1996.

Pooja S, Agrawal RP, Nyati P, Savita V, Phadnis P. Analgesic activity of piper nigrum extract per se and its interaction with diclofenac sodium and pentazocine in albino mice. Internet Jour Pharmacol 2007; 5: 181-9.

Assi D, Azim A, Rahman A, Mahran S. Analgesic effects of tramadol-diclofenac combination and their interaction with sycostimulant drugs in mice and rats. Eur J Pharmacol 1996;312:132-8.

Raffa RB, Friderichs E, Reimann W, Shank RP, Codd EE, Vaught JL. Opioid and nonopioid components independently contribute to the mechanism of action of tramadol, an atypical opioid analgesic. J Pharmacol Exp Ther 1992; 260: 275-85.

Cheng JK, Lai YJ, Chen CC, Cheng CR, Chiou LC. Magnesium chloride and ruthenium red attenuate the antiallodynic effect of intrathecal gabapentin in arat model of postoperative pain. Anesthesiology 2003; 98: 1472-9.

Heughan CE, Sawynok J. The interaction between gabapentin and amitryptyline in the rat formalin test after systemic administration. Anesth Analg 2002; 94: 975-80.

Field MJ, Hughes J, Singh L. Further evidence for the role of the alpha2 delta subunit of voltage dependent calcium channels in models of neuropathic pain. Br J Pharmacol 2000; 13: 282-6.

Dickenson D, Sullivan AF. Peripheral origins and central modulation of subcutaneous formalin induced activity of rat dorsal horn neurons. Neurosci Lett 1987; 83: 207-11.

Shannon HE, Eberle EL, Peters SC. Comparison of the effects of anticonvulsant drugs with diverse mechanisms of action in the formalin test in rats. Neuropharmacology 2005;48:1012-20.

Carlton SM, Zhou S. Attenuation of formalin induced nociceptive behaviors following local peripheral injection of gabapentin. Pain 1998; 76: 201-7.

Feng Y, Cui M, Willis WD. Gabapentin markedly reduces acetic acid induced visceral nociception. Anesthesiology 2003; 98: 131-9.

Blackburn MG, Ibsen N, Erichsen HK. A comparison of the antinociceptive effects of voltage activated Na+ channel blockers in the formalin test. Eur J Pharmacol 2002; 445: 231-8.

References

.

Maizes M, Mccarberg B. Antidepressant and antiepileptic drugs for chronic noncancer pain. Am Fam Physician 2005; 71: 483-90.

Merskey H, Albe-Fessard DG, Bonica JJ, Carmon A, Dubner R, Kerr FWL et al. Pain terms a list with definitions and notes on usage. Pain 1979; 6: 249-52.

Arrie K, Jones SC. Efficacy of duloxitine, a potent and balanced serotonergic and noradrenergic reuptake inhibitor, in inflammatory and acute pain models in rodents. J Pharmacol Exp Ther 2005; 313: 726-32

Pandi PV, Nagappa AN. Effect of acute and chronic treatment of losartan potassium on tailflick response in mice. Ind J Pharmacol 2006; 38: 281-2.

Vogel HG, Vogel WGH, editors, Drug discovery and evaluation-pharmacological assays. 2nd ed. New York: Verlog Springer publication;1996.

Christian D, Miranda HF, Raquel P, Mases A, Eulalia P. Synergistic interaction between dexamethasone and tramadol in a murine model of acute visceral pain. Fundamental Clin Pharmacol 2007; 21: 515-20.

Miranda HF, Pelissier T, Pinardi G. Involvement of adrenergic, serotonergic and opioid mechanisms in tramadol –induced antinociception in mice. Analgesia 1999; 4: 1-7.

Hernandez GC, Soto VG, Ortiz MI. Pinacidil increases diclofenac antinociception in the formalin test. Proc West Pharmacol Soc 2005; 48: 55-8.

Vogel HG, Vogel WGH, editors, Drug discovery and evaluation-pharmacological assays. 2nd ed. New York: Verlog Springer publication;1996.

Pooja S, Agrawal RP, Nyati P, Savita V, Phadnis P. Analgesic activity of piper nigrum extract per se and its interaction with diclofenac sodium and pentazocine in albino mice. Internet Jour Pharmacol 2007; 5: 181-9.

Assi D, Azim A, Rahman A, Mahran S. Analgesic effects of tramadol-diclofenac combination and their interaction with sycostimulant drugs in mice and rats. Eur J Pharmacol 1996;312:132-8.

Raffa RB, Friderichs E, Reimann W, Shank RP, Codd EE, Vaught JL. Opioid and nonopioid components independently contribute to the mechanism of action of tramadol, an atypical opioid analgesic. J Pharmacol Exp Ther 1992; 260: 275-85.

Cheng JK, Lai YJ, Chen CC, Cheng CR, Chiou LC. Magnesium chloride and ruthenium red attenuate the antiallodynic effect of intrathecal gabapentin in arat model of postoperative pain. Anesthesiology 2003; 98: 1472-9.

Heughan CE, Sawynok J. The interaction between gabapentin and amitryptyline in the rat formalin test after systemic administration. Anesth Analg 2002; 94: 975-80.

Field MJ, Hughes J, Singh L. Further evidence for the role of the alpha2 delta subunit of voltage dependent calcium channels in models of neuropathic pain. Br J Pharmacol 2000; 13: 282-6.

Dickenson D, Sullivan AF. Peripheral origins and central modulation of subcutaneous formalin induced activity of rat dorsal horn neurons. Neurosci Lett 1987; 83: 207-11.

Shannon HE, Eberle EL, Peters SC. Comparison of the effects of anticonvulsant drugs with diverse mechanisms of action in the formalin test in rats. Neuropharmacology 2005;48:1012-20.

Carlton SM, Zhou S. Attenuation of formalin induced nociceptive behaviors following local peripheral injection of gabapentin. Pain 1998; 76: 201-7.

Feng Y, Cui M, Willis WD. Gabapentin markedly reduces acetic acid induced visceral nociception. Anesthesiology 2003; 98: 131-9.

Blackburn MG, Ibsen N, Erichsen HK. A comparison of the antinociceptive effects of voltage activated Na+ channel blockers in the formalin test. Eur J Pharmacol 2002; 445: 231-8.

References

.

Maizes M, Mccarberg B. Antidepressant and antiepileptic drugs for chronic noncancer pain. Am Fam Physician 2005; 71: 483-90.

Merskey H, Albe-Fessard DG, Bonica JJ, Carmon A, Dubner R, Kerr FWL et al. Pain terms a list with definitions and notes on usage. Pain 1979; 6: 249-52.

Arrie K, Jones SC. Efficacy of duloxitine, a potent and balanced serotonergic and noradrenergic reuptake inhibitor, in inflammatory and acute pain models in rodents. J Pharmacol Exp Ther 2005; 313: 726-32

Pandi PV, Nagappa AN. Effect of acute and chronic treatment of losartan potassium on tailflick response in mice. Ind J Pharmacol 2006; 38: 281-2.

Vogel HG, Vogel WGH, editors, Drug discovery and evaluation-pharmacological assays. 2nd ed. New York: Verlog Springer publication;1996.

Christian D, Miranda HF, Raquel P, Mases A, Eulalia P. Synergistic interaction between dexamethasone and tramadol in a murine model of acute visceral pain. Fundamental Clin Pharmacol 2007; 21: 515-20.

Miranda HF, Pelissier T, Pinardi G. Involvement of adrenergic, serotonergic and opioid mechanisms in tramadol –induced antinociception in mice. Analgesia 1999; 4: 1-7.

Hernandez GC, Soto VG, Ortiz MI. Pinacidil increases diclofenac antinociception in the formalin test. Proc West Pharmacol Soc 2005; 48: 55-8.

Vogel HG, Vogel WGH, editors, Drug discovery and evaluation-pharmacological assays. 2nd ed. New York: Verlog Springer publication;1996.

Pooja S, Agrawal RP, Nyati P, Savita V, Phadnis P. Analgesic activity of piper nigrum extract per se and its interaction with diclofenac sodium and pentazocine in albino mice. Internet Jour Pharmacol 2007; 5: 181-9.

Assi D, Azim A, Rahman A, Mahran S. Analgesic effects of tramadol-diclofenac combination and their interaction with sycostimulant drugs in mice and rats. Eur J Pharmacol 1996;312:132-8.

Raffa RB, Friderichs E, Reimann W, Shank RP, Codd EE, Vaught JL. Opioid and nonopioid components independently contribute to the mechanism of action of tramadol, an atypical opioid analgesic. J Pharmacol Exp Ther 1992; 260: 275-85.

Cheng JK, Lai YJ, Chen CC, Cheng CR, Chiou LC. Magnesium chloride and ruthenium red attenuate the antiallodynic effect of intrathecal gabapentin in arat model of postoperative pain. Anesthesiology 2003; 98: 1472-9.

Heughan CE, Sawynok J. The interaction between gabapentin and amitryptyline in the rat formalin test after systemic administration. Anesth Analg 2002; 94: 975-80.

Field MJ, Hughes J, Singh L. Further evidence for the role of the alpha2 delta subunit of voltage dependent calcium channels in models of neuropathic pain. Br J Pharmacol 2000; 13: 282-6.

Dickenson D, Sullivan AF. Peripheral origins and central modulation of subcutaneous formalin induced activity of rat dorsal horn neurons. Neurosci Lett 1987; 83: 207-11.

Shannon HE, Eberle EL, Peters SC. Comparison of the effects of anticonvulsant drugs with diverse mechanisms of action in the formalin test in rats. Neuropharmacology 2005;48:1012-20.

Carlton SM, Zhou S. Attenuation of formalin induced nociceptive behaviors following local peripheral injection of gabapentin. Pain 1998; 76: 201-7.

Feng Y, Cui M, Willis WD. Gabapentin markedly reduces acetic acid induced visceral nociception. Anesthesiology 2003; 98: 131-9.

Blackburn MG, Ibsen N, Erichsen HK. A comparison of the antinociceptive effects of voltage activated Na+ channel blockers in the formalin test. Eur J Pharmacol 2002; 445: 231-8.

References

.

Maizes M, Mccarberg B. Antidepressant and antiepileptic drugs for chronic noncancer pain. Am Fam Physician 2005; 71: 483-90.

Merskey H, Albe-Fessard DG, Bonica JJ, Carmon A, Dubner R, Kerr FWL et al. Pain terms a list with definitions and notes on usage. Pain 1979; 6: 249-52.

Arrie K, Jones SC. Efficacy of duloxitine, a potent and balanced serotonergic and noradrenergic reuptake inhibitor, in inflammatory and acute pain models in rodents. J Pharmacol Exp Ther 2005; 313: 726-32

Pandi PV, Nagappa AN. Effect of acute and chronic treatment of losartan potassium on tailflick response in mice. Ind J Pharmacol 2006; 38: 281-2.

Vogel HG, Vogel WGH, editors, Drug discovery and evaluation-pharmacological assays. 2nd ed. New York: Verlog Springer publication;1996.

Christian D, Miranda HF, Raquel P, Mases A, Eulalia P. Synergistic interaction between dexamethasone and tramadol in a murine model of acute visceral pain. Fundamental Clin Pharmacol 2007; 21: 515-20.

Miranda HF, Pelissier T, Pinardi G. Involvement of adrenergic, serotonergic and opioid mechanisms in tramadol –induced antinociception in mice. Analgesia 1999; 4: 1-7.

Hernandez GC, Soto VG, Ortiz MI. Pinacidil increases diclofenac antinociception in the formalin test. Proc West Pharmacol Soc 2005; 48: 55-8.

Vogel HG, Vogel WGH, editors, Drug discovery and evaluation-pharmacological assays. 2nd ed. New York: Verlog Springer publication;1996.

Pooja S, Agrawal RP, Nyati P, Savita V, Phadnis P. Analgesic activity of piper nigrum extract per se and its interaction with diclofenac sodium and pentazocine in albino mice. Internet Jour Pharmacol 2007; 5: 181-9.

Assi D, Azim A, Rahman A, Mahran S. Analgesic effects of tramadol-diclofenac combination and their interaction with sycostimulant drugs in mice and rats. Eur J Pharmacol 1996;312:132-8.

Raffa RB, Friderichs E, Reimann W, Shank RP, Codd EE, Vaught JL. Opioid and nonopioid components independently contribute to the mechanism of action of tramadol, an atypical opioid analgesic. J Pharmacol Exp Ther 1992; 260: 275-85.

Cheng JK, Lai YJ, Chen CC, Cheng CR, Chiou LC. Magnesium chloride and ruthenium red attenuate the antiallodynic effect of intrathecal gabapentin in arat model of postoperative pain. Anesthesiology 2003; 98: 1472-9.

Heughan CE, Sawynok J. The interaction between gabapentin and amitryptyline in the rat formalin test after systemic administration. Anesth Analg 2002; 94: 975-80.

Field MJ, Hughes J, Singh L. Further evidence for the role of the alpha2 delta subunit of voltage dependent calcium channels in models of neuropathic pain. Br J Pharmacol 2000; 13: 282-6.

Dickenson D, Sullivan AF. Peripheral origins and central modulation of subcutaneous formalin induced activity of rat dorsal horn neurons. Neurosci Lett 1987; 83: 207-11.

Shannon HE, Eberle EL, Peters SC. Comparison of the effects of anticonvulsant drugs with diverse mechanisms of action in the formalin test in rats. Neuropharmacology 2005;48:1012-20.

Carlton SM, Zhou S. Attenuation of formalin induced nociceptive behaviors following local peripheral injection of gabapentin. Pain 1998; 76: 201-7.

Feng Y, Cui M, Willis WD. Gabapentin markedly reduces acetic acid induced visceral nociception. Anesthesiology 2003; 98: 131-9.

Blackburn MG, Ibsen N, Erichsen HK. A comparison of the antinociceptive effects of voltage activated Na+ channel blockers in the formalin test. Eur J Pharmacol 2002; 445: 231-8.

References

.

Maizes M, Mccarberg B. Antidepressant and antiepileptic drugs for chronic noncancer pain. Am Fam Physician 2005; 71: 483-90.

Merskey H, Albe-Fessard DG, Bonica JJ, Carmon A, Dubner R, Kerr FWL et al. Pain terms a list with definitions and notes on usage. Pain 1979; 6: 249-52.

Arrie K, Jones SC. Efficacy of duloxitine, a potent and balanced serotonergic and noradrenergic reuptake inhibitor, in inflammatory and acute pain models in rodents. J Pharmacol Exp Ther 2005; 313: 726-32

Pandi PV, Nagappa AN. Effect of acute and chronic treatment of losartan potassium on tailflick response in mice. Ind J Pharmacol 2006; 38: 281-2.

Vogel HG, Vogel WGH, editors, Drug discovery and evaluation-pharmacological assays. 2nd ed. New York: Verlog Springer publication;1996.

Christian D, Miranda HF, Raquel P, Mases A, Eulalia P. Synergistic interaction between dexamethasone and tramadol in a murine model of acute visceral pain. Fundamental Clin Pharmacol 2007; 21: 515-20.

Miranda HF, Pelissier T, Pinardi G. Involvement of adrenergic, serotonergic and opioid mechanisms in tramadol –induced antinociception in mice. Analgesia 1999; 4: 1-7.

Hernandez GC, Soto VG, Ortiz MI. Pinacidil increases diclofenac antinociception in the formalin test. Proc West Pharmacol Soc 2005; 48: 55-8.

Vogel HG, Vogel WGH, editors, Drug discovery and evaluation-pharmacological assays. 2nd ed. New York: Verlog Springer publication;1996.

Pooja S, Agrawal RP, Nyati P, Savita V, Phadnis P. Analgesic activity of piper nigrum extract per se and its interaction with diclofenac sodium and pentazocine in albino mice. Internet Jour Pharmacol 2007; 5: 181-9.

Assi D, Azim A, Rahman A, Mahran S. Analgesic effects of tramadol-diclofenac combination and their interaction with sycostimulant drugs in mice and rats. Eur J Pharmacol 1996;312:132-8.

Raffa RB, Friderichs E, Reimann W, Shank RP, Codd EE, Vaught JL. Opioid and nonopioid components independently contribute to the mechanism of action of tramadol, an atypical opioid analgesic. J Pharmacol Exp Ther 1992; 260: 275-85.

Cheng JK, Lai YJ, Chen CC, Cheng CR, Chiou LC. Magnesium chloride and ruthenium red attenuate the antiallodynic effect of intrathecal gabapentin in arat model of postoperative pain. Anesthesiology 2003; 98: 1472-9.

Heughan CE, Sawynok J. The interaction between gabapentin and amitryptyline in the rat formalin test after systemic administration. Anesth Analg 2002; 94: 975-80.

Field MJ, Hughes J, Singh L. Further evidence for the role of the alpha2 delta subunit of voltage dependent calcium channels in models of neuropathic pain. Br J Pharmacol 2000; 13: 282-6.

Dickenson D, Sullivan AF. Peripheral origins and central modulation of subcutaneous formalin induced activity of rat dorsal horn neurons. Neurosci Lett 1987; 83: 207-11.

Shannon HE, Eberle EL, Peters SC. Comparison of the effects of anticonvulsant drugs with diverse mechanisms of action in the formalin test in rats. Neuropharmacology 2005;48:1012-20.

Carlton SM, Zhou S. Attenuation of formalin induced nociceptive behaviors following local peripheral injection of gabapentin. Pain 1998; 76: 201-7.

Feng Y, Cui M, Willis WD. Gabapentin markedly reduces acetic acid induced visceral nociception. Anesthesiology 2003; 98: 131-9.

Blackburn MG, Ibsen N, Erichsen HK. A comparison of the antinociceptive effects of voltage activated Na+ channel blockers in the formalin test. Eur J Pharmacol 2002; 445: 231-8.

References

.

Maizes M, Mccarberg B. Antidepressant and antiepileptic drugs for chronic noncancer pain. Am Fam Physician 2005; 71: 483-90.

Merskey H, Albe-Fessard DG, Bonica JJ, Carmon A, Dubner R, Kerr FWL et al. Pain terms a list with definitions and notes on usage. Pain 1979; 6: 249-52.

Arrie K, Jones SC. Efficacy of duloxitine, a potent and balanced serotonergic and noradrenergic reuptake inhibitor, in inflammatory and acute pain models in rodents. J Pharmacol Exp Ther 2005; 313: 726-32

Pandi PV, Nagappa AN. Effect of acute and chronic treatment of losartan potassium on tailflick response in mice. Ind J Pharmacol 2006; 38: 281-2.

Vogel HG, Vogel WGH, editors, Drug discovery and evaluation-pharmacological assays. 2nd ed. New York: Verlog Springer publication;1996.

Christian D, Miranda HF, Raquel P, Mases A, Eulalia P. Synergistic interaction between dexamethasone and tramadol in a murine model of acute visceral pain. Fundamental Clin Pharmacol 2007; 21: 515-20.

Miranda HF, Pelissier T, Pinardi G. Involvement of adrenergic, serotonergic and opioid mechanisms in tramadol –induced antinociception in mice. Analgesia 1999; 4: 1-7.

Hernandez GC, Soto VG, Ortiz MI. Pinacidil increases diclofenac antinociception in the formalin test. Proc West Pharmacol Soc 2005; 48: 55-8.

Vogel HG, Vogel WGH, editors, Drug discovery and evaluation-pharmacological assays. 2nd ed. New York: Verlog Springer publication;1996.

Pooja S, Agrawal RP, Nyati P, Savita V, Phadnis P. Analgesic activity of piper nigrum extract per se and its interaction with diclofenac sodium and pentazocine in albino mice. Internet Jour Pharmacol 2007; 5: 181-9.

Assi D, Azim A, Rahman A, Mahran S. Analgesic effects of tramadol-diclofenac combination and their interaction with sycostimulant drugs in mice and rats. Eur J Pharmacol 1996;312:132-8.

Raffa RB, Friderichs E, Reimann W, Shank RP, Codd EE, Vaught JL. Opioid and nonopioid components independently contribute to the mechanism of action of tramadol, an atypical opioid analgesic. J Pharmacol Exp Ther 1992; 260: 275-85.

Cheng JK, Lai YJ, Chen CC, Cheng CR, Chiou LC. Magnesium chloride and ruthenium red attenuate the antiallodynic effect of intrathecal gabapentin in arat model of postoperative pain. Anesthesiology 2003; 98: 1472-9.

Heughan CE, Sawynok J. The interaction between gabapentin and amitryptyline in the rat formalin test after systemic administration. Anesth Analg 2002; 94: 975-80.

Field MJ, Hughes J, Singh L. Further evidence for the role of the alpha2 delta subunit of voltage dependent calcium channels in models of neuropathic pain. Br J Pharmacol 2000; 13: 282-6.

Dickenson D, Sullivan AF. Peripheral origins and central modulation of subcutaneous formalin induced activity of rat dorsal horn neurons. Neurosci Lett 1987; 83: 207-11.

Shannon HE, Eberle EL, Peters SC. Comparison of the effects of anticonvulsant drugs with diverse mechanisms of action in the formalin test in rats. Neuropharmacology 2005;48:1012-20.

Carlton SM, Zhou S. Attenuation of formalin induced nociceptive behaviors following local peripheral injection of gabapentin. Pain 1998; 76: 201-7.

Feng Y, Cui M, Willis WD. Gabapentin markedly reduces acetic acid induced visceral nociception. Anesthesiology 2003; 98: 131-9.

Blackburn MG, Ibsen N, Erichsen HK. A comparison of the antinociceptive effects of voltage activated Na+ channel blockers in the formalin test. Eur J Pharmacol 2002; 445: 231-8.

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