Top

BMC Musculoskeletal Disorders

Published in:

Open Access 01-12-2008 | Research article

Analgesic effect of percutaneously absorbed non-steroidal anti-inflammatory drugs: an experimental study in a rat acute inflammation model

Authors: Miho Sekiguchi, Masayoshi Shirasaka, Shin-ichi Konno, Shin-ichi Kikuchi

Published in: BMC Musculoskeletal Disorders | Issue 1/2008

Abstract

Background

External medication that is absorbed percutaneously may be used to reduce inflammation and relieve pain from acute injuries such as ankle sprains and bruises. The plaster method of percutaneous absorption for non-steroidal anti-inflammatory drugs (NSAIDs) was established in Japan in 1988. However, due to the possibility of a placebo effect, the efficacy of this method remains unclear. This experimental study was conducted to control for the placebo effect and to study the efficacy of the plaster method in relieving pain by using a rat model of inflammation.

Methods

Male Wistar-Imamichi rats were used. A yeast suspension was injected into the right hind paw to induce inflammation. A sheet (2.0 × 1.75 cm) containing the drug was adhered to the inflamed paw. Five treatment groups were used, and each sheet contained a single drug: loxoprofen sodium (loxoprofen-Na) (2.5 mg); felbinac (1.75 mg); indomethacin (1.75 mg); ketoprofen (0.75 mg); or base only (control, 0 mg). Mechanical pain threshold, expression of c-Fos in the dorsal horn, and amount of prostaglandin (PG) E₂ in the inflamed paw were evaluated.

Results

Pain threshold increased after treatment, and was significantly increased in the loxoprofen-Na group compared with the control group (p < 0.05). Amounts of PGE₂ were significantly decreased in the loxoprofen-Na and indomethacin groups compared with the control group (p < 0.05). Expression of c-Fos was significantly decreased in the loxoprofen-Na group compared with the control group (p < 0.05).

Conclusion

Percutaneously absorbed NSAIDs have an analgesic effect, inhibit expression of c-Fos in the dorsal horn, and reduce PGE₂ in inflamed tissue, indicating the efficacy of this method of administration for acute inflammation and localized pain.

Available only for authorised users

Minami T, Uda R, Horiguchi S, Ito S, Hyodo M, Hayaishi O: Allodynia evoked by intrathecal administration of prostaglandin E2 to conscious mice. Pain. 1994, 57: 217-223. 10.1016/0304-3959(94)90226-7.CrossRefPubMed

Hunt SP, Pini A, Evan G: Induction of c-fos-like protein in spinal cord neurons following sensory stimulation. Nature. 1987, 328: 632-634. 10.1038/328632a0.CrossRefPubMed

Menetrey D, Gannon A, Levine JD, Basbaum AI: Expression of c-fos protein in interneurons and projection neurons of the rat spinal cord in response to noxious somatic, articular, and visceral stimulation. J Comp Neurol. 1989, 285: 177-195. 10.1002/cne.902850203.CrossRefPubMed

Morgan JI, Curran T: Stimulus-transcription coupling in the nervous system: involvement of the inducible proto-oncogenes fos and jun. Annu Rev Neurosci. 1991, 14: 421-451. 10.1146/annurev.ne.14.030191.002225.CrossRefPubMed

Randall LO, Selitto JJ: A method for measurement of analgesic activity on inflamed tissue. Arch Int Pharmacodyn Ther. 1957, 111: 409-419.PubMed

Winter CA, Flataker L: Reaction threshold to pressure in edematous hindpaws of rats and responses to analgesic drugs. J Pharmacol Exp Ther. 1965, 150: 165-171.PubMed

Mizobuchi S, Takahashi T, Yokoyama M, Nakatsuka H, Morita K: The formalin teat: time course and location changes of c-fos mRNA and FOS protein expression. Anesthesiology. 2003, 99: A939-

Molander C, Hongpaisan J, Grant G: Changing pattern of c-fos expression in spinal cord neurons after electrical stimulation of the chronically injured sciatic nerve in the rat. Neuroscience. 1992, 50: 223-236. 10.1016/0306-4522(92)90394-H.CrossRefPubMed

Rainsford KD: Anti-inflammatory drugs in the 21st century. Subcell Biochem. 2007, 42: 3-27.CrossRefPubMed

10.

Singh P, Roberts MS: Skin permeability and local tissue concentrations of nonsteroidal anti-inflammatory drugs after topical application. J Pharmacol Exp Ther. 1994, 268: 144-151.PubMed

11.

Buritova J, Honore P, Chapman V, Besson JM: Concurrent reduction of inflammation and spinal Fos-LI neurons by systemic diclofenac in the rat. Neurosci Lett. 1995, 188: 175-178. 10.1016/0304-3940(95)11426-W.CrossRefPubMed

12.

Lima D, Avelino A, Coimbra A: Differential activation of c-fos in spinal neurons by distinct classes of noxious stimuli. Neuroreport. 1993, 4: 747-750. 10.1097/00001756-199306000-00037.CrossRefPubMed

13.

Tokunaga A, Doi M, Senba E: Effects of local anaesthesia on formalin-induced Fos expression in the rat dorsal horn. Neuroreport. 1995, 27: 2301-2304.CrossRef

14.

Presley RW, Menetrey D, Levine JD, Basbaum AI: Systemic morphine suppresses noxious stimulus-evoked Fos protein-like immunoreactivity in the rat spinal cord. J Neurosci. 1990, 10: 323-335.PubMed

15.

Naranjo JR, Mellström B, Achaval M, Sassone-Corsi P: Molecular pathways of pain: Fos/Jun-mediated activation of a noncanonical AP-1 site in the prodynorphin gene. Neuron. 1991, 6: 607-617. 10.1016/0896-6273(91)90063-6.CrossRefPubMed

16.

Sonnenberg JL, Rauscher FJ, Morgan JI, Curran T: Regulation of proenkephalin by Fos and Jun. Science. 1989, 246: 1622-1625. 10.1126/science.2512642.CrossRefPubMed

17.

Carrive P, Meyer-Carrive I: Changes in formalin-evoked spinal Fos expression and nociceptive behavior after oral administration of bufferin A(aspirin) and L-5409709(ibuprofen+caffeine+paracetamol). Pain. 1997, 70: 253-266. 10.1016/S0304-3959(97)03325-8.CrossRefPubMed

18.

Lima D, Avelino A, Coimbra A: Differential activation of c-fos in spinal neurons by distinct classes of noxious stimuli. Neuroreport. 1993, 4: 747-750. 10.1097/00001756-199306000-00037.CrossRefPubMed

19.

Buritova J, Besson JM: Effects of flurbiprofen and its enantiomers on the spinal c-Fos protein expression induced by noxious heat stimuli in the anaesthetized rat. Eur J Phamacol. 2000, 406: 59-67. 10.1016/S0014-2999(00)00650-6.CrossRef

20.

Honore P, Buritova J, Besson JM: Carrageenin-evoked c-Fos expression in rat lumbar spinal cord: the effects of indomethacin. Eur J Phamacol. 1995, 272: 249-259. 10.1016/0014-2999(94)00656-R.CrossRef

21.

Buritova J, Honore P, Besson JM: Ketoprofen produces profound inhibition of spinal c-Fos protein expression resulting from an inflammatory stimulus but not from noxious heat. Pain. 1996, 67: 379-389. 10.1016/0304-3959(96)03138-7.CrossRefPubMed

The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2474/9/15/prepub

Title: Analgesic effect of percutaneously absorbed non-steroidal anti-inflammatory drugs: an experimental study in a rat acute inflammation model
Authors: Miho Sekiguchi
Masayoshi Shirasaka
Shin-ichi Konno
Shin-ichi Kikuchi
Publication date: 01-12-2008
Publisher: BioMed Central
Published in: BMC Musculoskeletal Disorders / Issue 1/2008
Electronic ISSN: 1471-2474
DOI: https://doi.org/10.1186/1471-2474-9-15

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Analgesic effect of percutaneously absorbed non-steroidal anti-inflammatory drugs: an experimental study in a rat acute inflammation model

Abstract

Background

Methods

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusion

Please log in to get access to this content

Other articles of this Issue 1/2008

A new short uncemented, proximally fixed anatomic femoral implant with a prominent lateral flare: design rationals and study design of an international clinical trial

Fatigue in osteoarthritis: a qualitative study

Are the determinants of vertebral endplate changes and severe disc degeneration in the lumbar spine the same? A magnetic resonance imaging study in middle-aged male workers

Physical inactivity is associated with chronic musculoskeletal complaints 11 years later: results from the Nord-Trøndelag Health Study

A new tool for mini-open carpal tunnel release – the PSU retractor

Self-reported hard physical work combined with heavy smoking or overweight may result in so-called Modic changes