Korean J Pain.  2019 Oct;32(4):256-263. 10.3344/kjp.2019.32.4.256.

Antinociceptive and anti-inflammatory effects of N-acetylcysteine and verapamil in Wistar rats

• Elberry AA
• Sharkawi S
• Wahba MR

• KMID: 2462835
• DOI: http://doi.org/10.3344/kjp.2019.32.4.256

Abstract

BACKGROUND
Antinociceptive anti-inflammatory drugs have many adverse effects. The goal of this investigation is to study the probable anti-inflammatory and analgesic effects of verapamil and N-acetylcysteine (NAC) in experimental rats.
METHODS
Adult male Wistar rats were randomly divided into 4 groups in the antinociceptive study, each containing 6 rats; the normal control group, which received saline (1 mL/kg); the diclofenac group, which received diclofenac sodium (5 mg/kg); the NAC group, which received NAC (125 mg/kg); and the verapamil group, which received verapamil (8 mg/kg). In the anti-inflammatory study, 5 groups were used, the 4 previous groups with the addition of an edema control group, received saline and were subjected to formalin test. Hot plate latency time was recorded for antinociceptive evaluation. Paw edema thickness and biochemical parameters were recorded for anti-inflammatory evaluation.
RESULTS
Administration of NAC showed significant prolongation of hot plate latency time at 1 hour when compared to the control group while verapamil showed a significant prolongation of hot plate latency time at 1 and 2 hours when compared to the control group and NAC group values. Administration of NAC and verapamil significantly decreased paw edema thickness at 2, 4, and 8 hours when compared to edema control values. Regarding biochemical markers, NAC and verapamil significantly decreased serum nitric oxide synthase, C-reactive protein, and cyclooxygenase-2 levels compared to the edema control value. In accordance, a marked improvement of histopathological findings was observed with both drugs.
CONCLUSIONS
NAC and verapamil have antinociceptive and anti-inflammatory effects comparable to diclofenac sodium.

Keyword

Anti-Inflammatory Agents; Antinociceptive; Cyclooxygenase 2; Diclofenac; Edema; Nitric Oxide Synthase; Pain Measurement; Verapamil

MeSH Terms

Acetylcysteine*
Adult
Animals
Anti-Inflammatory Agents
Biomarkers
C-Reactive Protein
Cyclooxygenase 2
Diclofenac
Edema
Humans
Male
Nitric Oxide Synthase
Pain Measurement
Rats
Rats, Wistar*
Verapamil*
Acetylcysteine
Anti-Inflammatory Agents
Biomarkers
C-Reactive Protein
Cyclooxygenase 2
Diclofenac
Nitric Oxide Synthase
Verapamil

Figure

• 

  Fig. 1 The effect of N-acetylcysteine (NAC) and verapamil on formalin-induced paw edema after 1, 2, 4, and 8 hours of formalin injection. Data are expressed as mean ± standard error of the mean. aSignificantly different from normal control value. bSignificantly different from Paw edema value. cSignificantly different from diclofenac value (P < 0.05 is considered significant).

• 

  Fig. 2 The effect of 2 doses of diclofenac sodium, N-acetylcysteine (NAC), and verapamil on the formalin-induced paw edema serum alterations of C-reactive protein (CRP) (A), and cyclooxygenase-2 (COX-2) (B). Data are expressed as mean ± standard error of the mean (P < 0.05 is considered significant). aSignificantly different from normal control value. bSignificantly different from Paw edema value.

• 

  Fig. 3 (A) Section in rat paw of normal control group showing normal dermal and epidermal architecture with no signs of edema or inflammatory cells. (B) Section in paw of rat injected with formalin (group II): showing deep dermal layer dispersed by edema (black arrows) and infiltrated by abundant mononuclear inflammatory cells (green arrows = macrophages, blue arrows = lymphocytes, and yellow arrow = neutrophils) and congestion (red arrows). (C, D) Sections in paw of rats received diclofenac sodium showing edema (black arrows), few inflammatory cells (yellow arrows) and congestion (red arrows) but somewhat less than paw edema group. (E, F) Sections in paw of rats received N-acetylcysteine showing subsiding edema (black arrow) and very few inflammatory cells (yellow arrows) with congestion (red arrows) but less than group paw edema group. (G, H) Section in paw of rats which treated by verapamil showing subsiding congestion (red arrows) and edema (black arrow) with congestion (red arrows), and few inflammatory (blue arrows = lymphocytes, and yellow arrows = neutrophils) with macrophages (green arrows) that engulf debris and necrosed tissue (H&E, × 100).

• 

  Fig. 4 The effect of diclofenac, N-acetylcysteine (NAC), and verapamil on formalin-induced paw edema histopathological scoring. Data are expressed as mean ± standard error of the mean. aSignificantly different from Paw edema value; bSignificantly different from diclofenac value (P < 0.05 is considered significant).

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