Neuroinflammation in the pathophysiology of Parkinson’s disease and therapeutic evidence of anti-inflammatory drugs

Bassani, Taysa Bervian; Vital, Maria A.B.F.; Rauh, Laryssa K.

doi:10.1590/0004-282X20150057

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VIEWS AND REVIEWS • Arq. Neuro-Psiquiatr. 73 (7) • July 2015 • https://doi.org/10.1590/0004-282X20150057 copy

Neuroinflammation in the pathophysiology of Parkinson’s disease and therapeutic evidence of anti-inflammatory drugs

Neuroinflamação na patofisiologia da doença de Parkinson e evidências terapêuticas de drogas antiinflamatórias

Authorship SCIMAGO INSTITUTIONS RANKINGS

Parkinson’s disease (PD) is the second most common neurodegenerative disease affecting approximately 1.6% of the population over 60 years old. The cardinal motor symptoms are the result of progressive degeneration of substantia nigra pars compacta dopaminergic neurons which are involved in the fine motor control. Currently, there is no cure for this pathology and the cause of the neurodegeneration remains unknown. Several studies suggest the involvement of neuroinflammation in the pathophysiology of PD as well as a protective effect of anti-inflammatory drugs both in animal models and epidemiological studies, although there are controversial reports. In this review, we address evidences of involvement of inflammatory process and possible therapeutic usefulness of anti-inflammatory drugs in PD.

Parkinson’s disease; neuroinflammation; anti-inflammatory

Authors	Type of study	Participants	PD cases	RR/OR	95% CI	Drugs	Results
Chen et al.³⁴	Prospective cohort	142,902	415	0.55	0.32–0.96	Non-ASA NSAIDs	Reduction in PD risk for regular users of non-ASA NSAIDs
Chen et al.³⁴	Prospective cohort			0.56	0.86 - 1.09	ASA	Reduction in PD risk for regular users of non-ASA NSAIDs
Chen et al.³⁵	Prospective cohort	146,565	413	0.65	0.48–0.89	Ibuprofen	Reduction in PD risk for regular users of ibuprofen. This protective effect was not demonstrated for other NSAIDs, ASA or acetaminophen.
Chen et al.³⁵	Prospective cohort			0.78	0.60 –1.02	Non-ASA NSAIDs (including ibuprofen)
Etminan and Suissa³⁶	Case-control	-	-	1.49	1.11-2.01	NSAIDs	Current users of NSAIDs have shown a slightly higher risk of developing PD
Etminan and Suissa³⁶	Case-control			1.18	0.89-1.59	NSAIDs	Past users of NSAIDs did not have higher risk of PD
Hernán et al.³⁷	Case-control	7,896	1258	0.93	0.80–1.08	Non-ASA NSAIDs	Reduction in PD risk for regular users of non-ASA NSAIDs in men but not in women.
Bower et al.³⁸	Case-control	404	202	0.50	0.20–1.5	Non-ASA NSAIDs e SAIDs	Only a trend of reduction in PD risk for users of non-ASA NSAIDs and SAIDs
Ton et al.³⁹	Case-control	589	206	0.90	0.59–1.35	Non-ASA NSAIDs	No association was found between use of NSAIDs and reduction of PD risk.
				0.89	0.60 –1.32	Ibuprofen
				0.74	0.49 –1.12	ASA
Bornebroek et al.⁴⁰	Prospective cohort	6,512	88	1.50	0.95–2.37	Any NSAIDs	No association was found between use of any NSAIDs and the risk of developing PD
Wahner et al.⁴¹	Case-control	579	293	0.80	0.56 - 1.15	Regular ASA (≥2 pills/week)	Regular use of ASA showed a mild protective effect. The ASA effect was stronger in women, especially among long term regular users. A protective effect was observed for regular non-ASA NSAID users particularly those who reported ≥ 2 years of use.
				0.52	0.35 - 0.79	Regular Non-ASA NSAIDs
				0.44	0.26 - 0.74	≥2 years Non-ASA NSAIDs
				0.51	0.26 - 1.02	≥24 months ASA (women)
Etminan et al.⁴²	Retrospective cohort	697,078	5010	0.84	0.81–1.09	NSAIDs	No association was found between use of NSAIDs and reduction in PD risk.
Samii et al.⁴³	Meta-analysis of 11 observational studies	-	-	0.95	0.80 - 1.12	NSAIDs	NSAIDs do not seem to modify the risk of PD. Ibuprofen may have a slight protective effect.
				0.91	0.78 - 1.05	High-dose/long-duration NSAIDs
				1.08	0.93, 1.26	ASA
				0.76	0.65, 0.89	Ibuprofen
Gagne and Power⁴⁴	Meta-analysis of 7 studies	-	-	0.85	0.77–0.94	Non-ASA NSAIDs	Reduction of 15% in PD incidence among users of non-ASA NSAIDs with a similar effect for ibuprofen alone. In contrast, no protective effect was found for ASA or paracetamol.
				0.71	0.58–0.89	Non-ASA NSAIDs regular users
				0.79	0.59–1.07	Non-ASA NSAIDs long-term users
				0.75	0.64–0.89	Ibuprofen
				1.08	0.92–1.27	ASA
				1.06	0.87–1.30	Paracetamol
Rees et al.⁴⁵	Meta-analysis of 14 observational studies	-	-	0.87	0.73-1.04	Non-ASA NSAIDs	There were no association between use of any NSAIDs or ASA and the risk of developing PD. Exposure to non-ASA NSAIDs reduced the PD risk by 13% without statistical significance. Ibuprofen alone showed a 27% reduction in PD risk.
Rees et al.⁴⁵	Meta-analysis of 14 observational studies			0.73	0.63-0.85	Ibuprofen
Driver et al.⁴⁶	Case-control	22,007	1181	1.28	1.05-1.56	Absence of non-ASA NSAIDs use	Absence of non-ASA NSAIDs use was associated with an increased risk of PD. There was an increased risk of PD in men who had 1–2 years of regular non-ASA NSAID use. Positive association between PD and use of non-ASA. This association tended to disappear when analyses were limited to drug use ≥5 years before the disease diagnosis.
				1.35	1.07-1.70	1–2 years of regular use of non-ASA NSAID
				1.48	1.05-2.09	Use of non-ASA NSAIDs for 5 years or more
Manthriprag-ada et al.⁴⁷	Case-control	11,582	1931	0.97	0.82 - 1.14	ASA	No association was found between risk of PD and use of ASA or non-ASA NSAIDs when used shortly before the PD onset
Manthriprag-ada et al.⁴⁷	Case-control			0.97	0.86 - 1.09	Non-ASA NSAIDs
Becker et al.⁴⁸	Case-control	19,995	4026	0.94	0.83–1.07	NSAIDs long-term use	Long-term use of NSAIDs was associated with a slightly lower PD risk. Use of ASA or acetaminophen was not associated with a significant modification in the risk of PD.
				1.16	1.03–1.30	ASA long-term use
				1.15	1.02–1.30	Acetaminophen long-term use
Gao et al.⁴⁹	Prospective cohort followed by meta-analysis	136,197	291	0.62	0.42–0.93	Ibuprofen	Ibuprofen users have shown a significantly lower PD risk than nonusers with an additional dose-response relationship between tablets of ibuprofen taken per week and lower PD risk. This effect was not observed for ASA, other NSAIDs or paracetamol.
				0.99	0.78–1.26	ASA
				1.26	0.86–1.84	Non-ASA NSAIDs
				0.86	0.62–1.18	Paracetamol
				0.73	0.63–0.85	Ibuprofen (meta-analysis)

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[1] Correspondence: Taysa Bervian Bassani; Departamento de Farmacologia, UFPR; Rua Cel. Francisco H. dos Santos, 100; Centro Politécnico, Jardim das Américas; Caixa Postal 19031; 81531-980 Curitiba, PR, Brasil; E-mail: taysa_bassani@yahoo.com.br