A Comparison of the Antinociceptive Properties of SJP-005 and Morphine in Rats.

Joris C Verster,Thomas A Dahl,Jacqueline M Iversen,Andrew Scholey

doi:10.3390/pharmaceutics13020243

Joris C Verster, Thomas A Dahl + Show 2 more

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https://doi.org/10.3390/pharmaceutics13020243

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Abstract

SJP-005 (a combination of ketotifen and ibuprofen) is being developed as a potential treatment for pain and for opioid use disorder. It is therefore important to investigate the potential antinociceptive properties of SJP-005. Two studies were conducted to evaluate the potential effects of SJP-005 in rats. Study 1 applied the von Frey test to examine the antinociceptive effect of morphine with and without SJP-005 in adjuvant-induced hypersensitivity to tactile stimulation. In a double-blind, between-groups design, groups of rats (n = 10 each) received morphine at 3, 10, or 30 mg/kg bodyweight (bw) (subcutaneous injection) with or without SJP-005 (oral). Mechanic allodynia and paw volume were assessed before and after treatment. Study 2 utilized the hot plate test. Using a crossover design, groups of rats (n = 10 each) received either morphine at 3, 10, or 30 mg/kg bw (subcutaneous injection) preceded by oral administration of placebo (Week 1) or SJP-005 (Week 2). In Study 1, in the von Frey up-and-down test, Δ paw withdrawal responses in Group 1 (3 mg/kg bw morphine) were significantly lower compared to those in Group 4 (3 mg/kg bw morphine plus SJP-005), whereas the differences in Δ paw withdrawal between Group 2 and Group 5 (10 mg/kg bw morphine with and without SJP-005) and between Group 3 and Group 6 (10 mg/kg bw morphine with and without SJP-005) did not reach statistical difference. Trendline analysis of the dose–response relationship for the morphine + placebo groups and morphine + SJP-005 groups revealed no significant differences in the intercepts and slopes. In Study 2, no significant differences were observed on hot plate performance between morphine and morphine in combination with SJP-005. In conclusion, the findings in the von Frey up-and-down test (Study 1) suggest that animals can withstand higher levels of painful stimuli when SJP-005 is co-administered. This may also suggest a possible opioid sparing effect. However, in the hot plate test (Study 2), animals did not respond more adaptively to stronger painful stimuli after co-administering SJP-005. These observations warrant further investigation of the antinociceptive properties of SJP-005.

Highlights

Opioid withdrawal symptoms comprise a constellation of “flu-like” symptoms, including feeling sick, muscle spasms/twitching, feeling of coldness, heart pounding, aches and pains, insomnia/trouble sleeping, sweating, restlessness, gastrointestinal complaints, tremor, and anxiety or irritability. While opioid drugs such as morphine and oxycodone are effective for reducing acute pain and as anesthesia during surgery, these drugs have high potential for abuse and dependency. This may lead to prolonged opioid use which may result in opioid use disorder
Paw volume/thickness significantly increased after dosing in all seven groups (p < 0.0001), but no significant differences between the groups were found for edema (F(6,63) = 1.931, p = 0.089)
SJP-005 appeared to influence the antinociceptive properties of morphine when inflammatory pain was assessed via hypersensitivity to tactile stimuli in the von Frey upand-down test (Study 1)

Summary

Introduction

Opioid withdrawal symptoms comprise a constellation of “flu-like” symptoms, including feeling sick, muscle spasms/twitching, feeling of coldness, heart pounding, aches and pains, insomnia/trouble sleeping, sweating, restlessness, gastrointestinal complaints, tremor, and anxiety or irritability While opioid drugs such as morphine and oxycodone are effective for reducing acute pain and as anesthesia during surgery, these drugs have high potential for abuse and dependency. Previous research in rodents [12] suggests that SJP-005 is effective in significantly reducing opioid withdrawal signs after cessation of morphine treatment. The number of days it took to observe zero withdrawal signs was significantly shorter when SJP-005 was administered two days before morphine cessation [12] Taken together, these findings suggest that SJP-005 is a suitable candidate drug to be used for opioid withdrawal, and it deserves further investigation. It was hypothesized that the antinociceptive effects of SJP-005 in Study 1 might be accompanied by such an opioid sparing effect

Materials and Methods

Housing and Handling of Animals

Study 1

Study 2

Safety and Adverse Effects

Discussion