Levetiracetam synergises with common analgesics in producing antinociception in a mouse model of painful diabetic neuropathy

Micov, Ana; Tomić, Maja; Pecikoza, Uroš; Ugresic, N.; Stepanović-Petrović, Radica

doi:10.1016/j.phrs.2015.04.014

Cited by 15 publications

(10 citation statements)

References 62 publications

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“…In SNI rats, paracetamol had a significant antihypersensitivity effect at a low dose (50 mg/kg) that was subantinociceptive in sham‐operated animals. This finding is in line with an earlier study showing that 50 mg/kg of paracetamol reduced mechanical allodynia in neuropathic rats, and with a recent study that used a diabetic mouse model and showed that paracetamol (5‐100 mg/kg) alleviated diabetic nociceptive pain in a dose‐dependent manner . It is known that paracetamol is potentially hepatotoxic especially when used in high doses .…”

Section: Discussionsupporting

confidence: 91%

“…This finding is in line with an earlier study showing that 50 mg/kg of paracetamol reduced mechanical allodynia in neuropathic rats, 13 and with a recent study that used a diabetic mouse model and showed that paracetamol (5-100 mg/kg) alleviated diabetic nociceptive pain in a dose-dependent manner. 31 It is known that paracetamol is potentially hepatotoxic especially when used in high doses. 1 The finding of this study that a low dose of paracetamol that does not elevate hepatic enzymes in rats 13 alleviated neuropathic pain without increasing anxiety-like or anhedonic behavior may be relevant also for human medicine.…”

Section: Effect Of Paracetamol On Healthy Control Ratsmentioning

confidence: 99%

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Anxiety‐ and activity‐related effects of paracetamol on healthy and neuropathic rats

Chen

Wang

Pertovaara

et al. 2017

Pharmacology Res & Perspec

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Paracetamol has recently been suggested to affect emotion processing in addition to alleviating pain in humans. We investigated in adult male Hannover–Wistar rats whether acute intraperitoneally administrated paracetamol affects behavior in tests measuring anxiety, mood, motor activity, and memory. Unoperated rats received saline or a low (50 mg/kg) or high (300 mg/kg) dose of paracetamol, while rats with a spared nerve injury (SNI) model of neuropathy and sham‐operated rats received saline or the low dose of paracetamol. Rats were tested on open‐field (OFT), elevated plus‐maze (EPM), light‐dark box (LDB), novel‐object recognition (NOR), sucrose preference, rotarod, and monofilament tests. In unoperated rats, both the low and high dose of paracetamol reduced line crossings, and grooming time in the OFT, and novel preference in NOR. The high dose of paracetamol increased the time spent in the closed arm in EPM, reduced the number of rearings and leanings in OFT, the time spent in the light box in LDB, and sucrose preference. Paracetamol had no significant effect on the rotarod test measuring motor activity. The low dose of paracetamol suppressed mechanical pain hypersensitivity in SNI rats, without influencing pain behavior in sham‐operated rats. Saline‐ but not paracetamol‐treated SNI rats spent more time than sham‐operated rats in the closed arm in the EPM test. Together the results suggest that a high dose of paracetamol increases anxiety‐like and anhedonic behavior, and impairs recognition memory in unoperated controls, while in neuropathy, a low dose of paracetamol reduces nerve injury‐associated anxiety probably by reducing neuropathic pain.

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Section: Discussionsupporting

confidence: 91%

Section: Effect Of Paracetamol On Healthy Control Ratsmentioning

confidence: 99%

Anxiety‐ and activity‐related effects of paracetamol on healthy and neuropathic rats

Chen

Wang

Pertovaara

et al. 2017

Pharmacology Res & Perspec

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“…We think that the reason for this could due to the consideration that only 50% of diabetic patients were treated by aspirin which affected the results. However several studies reported positive effect for aspirin in reducing DN [13][14] . However, these studies studied the effects of combinations of aspirin with other drugs including levetiracetam or minocycline.…”

Section: Discussionmentioning

confidence: 98%

“…Micov et.al 14 showed that there was a synergism between levetiracetam and Ibuprofen /aspirin/paracetamol employing a model of painful diabetic neuropathy, the results were promising and it is possible to introduce a useful approach to treat patients with painful diabetic neuropathy.…”

Section: Introductionmentioning

confidence: 99%

Studying the Effect of Aspirin Treatment on Diabetic Neuropathy Among Diabetic Patients Attending Jordanian Royal Medical City

Al-Refai¹,

Madadha²,

Alfaqara³

et al. 2017

IRJPS

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“…From the literature, the doses of STZ used for diabetic induction in mice are varied. 5,6,7,8 Higher dose may induce lethal hyperglycemia that may prevent complete measurement and analysis. An appropriate dose of STZ is important, balancing the need to induce hyperglycemia and PDN, while at the same time reducing animal mortality rate.…”

Section: Introductionmentioning

confidence: 99%

The influence of long-term diabetes mellitus (DM) on pain response in mice: in vivo models of painful diabetic neuropathy (PDN)

et al. 2017

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Painful diabetic neuropathy (PDN) is a complication of long-term diabetes mellitus (DM) characterized by hyperalgesia and allodynia. In streptozotocin (STZ)-induced diabetic mice, higher dose of STZ and lengthened hyperglycemic condition results in better model of PDN. However, higher dose of STZ tend to induce mortality. The aim of the study was to evaluate the doses of STZ that caused PDN with less mortality rate and the timing of pain behavior development in mice model of PDN. BALB/c mice were divided into non-diabetic and STZ-induced diabetic group. The doses of STZ were started from 180 mg/kg BW i.p. Serum glucose levels were measured 7 days (one week) after induction. Mice with glucose levels ≥ 200 mg/dL were considered as diabetic. Pain behaviour was determined by four method i.e. hot plate, tail flick, von Frey filament and Randall Selitto tests, measured on week-0 (baseline), 1, 2, 3, 4 and 5. Data were presented as mean ± SEM. The mean differences between weeks were evaluated by One-Way ANOVA and the mean differences between two groups by independent t-test. STZ doses 180, 150 and 120 mg/kg BW caused 100% death and STZ 90 mg/kg BW failed to induce diabetic condition. STZ 110 mg/kg BW resulted in 0% mortality while it induced diabetes in 100% of the mice. Latency time toward thermal stimulus decreased to 5.8 ± 0.4 sec at 1 st week after the mice become diabetes (p<0.05) and it was continued to decrease until 4 th week. The same result was also showed in tail flick and Randal Selitto tests. The pain sensitivity determined by von Frey filament decreased to 1.37 ± 0.12 g at 1 st week (p<0.05) and continued to decrease until 5 th week. In conclusion, optimum dose of STZ to induce PDN was 110 mg/kg BW. Pain behaviour of diabetic group was observed at 1 st week after diabetes and continued until 5 th week. Perilaku nyeri kelompok diabetes teramati pada minggu pertama setelah diabetes dan berlanjut hingga minggu ke 5.

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Levetiracetam synergises with common analgesics in producing antinociception in a mouse model of painful diabetic neuropathy

Cited by 15 publications

References 62 publications

Anxiety‐ and activity‐related effects of paracetamol on healthy and neuropathic rats

Anxiety‐ and activity‐related effects of paracetamol on healthy and neuropathic rats

Studying the Effect of Aspirin Treatment on Diabetic Neuropathy Among Diabetic Patients Attending Jordanian Royal Medical City

The influence of long-term diabetes mellitus (DM) on pain response in mice: in vivo models of painful diabetic neuropathy (PDN)

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