id_925. NEUROPROTECTIVE POTENTIAL AND BEHAVIORAL EFFICACY OF A NEW AGENT IN A MURINE MODEL OF NEUROPATHIC PAIN
Mateusz Królewski1, Katarzyna Popiołek-Barczyk1, Magdalena Białoń1, Magdalena Maciuszek1, Maciej Degutis1, Marta Kędziora1, Ryszard Bugno2, Katarzyna Kaczorowska2, Andrzej Bojarski2, Katarzyna Starowicz1
1 Department of Neurochemistry, Maj Institute of Pharmacology, Polish Academy of Sciences, Smetna 12, 31-343 Kraków, Poland
2 Department of Chemistry, Maj Institute of Pharmacology, Polish Academy of Sciences, Smetna 12, 31-343 Kraków, Poland
INTRODUCTION: Neuropathic pain is a chronic condition typically resistant to conventional analgesics, including NSAIDs. This therapeutic resistance is driven by maladaptive neuroplasticity and glia-mediated chronic neuroinflammation, which perpetuate pain signaling independently of the initial peripheral insult. Although NSAIDs are not considered first-line treatments, they may be appropriate in select cases, particularly for patients with a mixed pain phenotype involving inflammatory mechanisms. Given this context, MIP001—an anti-inflammatory compound with a favorable safety profile—warrants further investigation as a potential therapeutic agent for neuropathic pain.
AIM(S): To determine the analgesic effects of MIP001 in a mouse model of neuropathic pain and to investigate its potential in vitro cytotoxicity and influence on glial-derived inflammatory mediators
METHOD(S): Neuropathic pain was induced in mice using the spared nerve injury (SNI) model. Mice received intraperitoneal (i.p.) MIP001 [20, 30 mg/kg], vehicle, or ibuprofen (30 mg/kg, positive control). Mechanical and thermal hypersensitivity were evaluated via von Frey and cold-plate tests, respectively. Additionally, in primary astroglial cultures, cytotoxicity (MTT test) and protein expression of inflammatory mediators (IL-1b, IL-6, IL-10, TNFα) were assessed following a 24h treatment with MIP001 [1, 10, and/or 50 µM] and/or lipopolysaccharide [100 ng/mL].
RESULTS: Our data showed that MIP001 dose- and time-dependently reduced mechanical and thermal hypersensitivity, providing significantly greater analgesia than ibuprofen. Furthermore, MIP001 did not alter protein expression or induce cytotoxicity in primary astrocytes, regardless of LPS treatment.
CONCLUSIONS: Our results showed that MIP001 has a significant analgesic effect on neuropathic pain, with an effect significantly greater than ibuprofen; however, the molecular mechanisms underlying this effect remain to be elucidated.
FINANCIAL SUPPORT: The study was supported by a programme coordinated by the Medical Research Agency, co-financed by the European Union under the NextGeneration EU initiative, within the framework of the National Recovery Plan, Component D, Investment D3.1.1 (project no. 2024/ABM/03/KPO/KPOD.07.07-IW.07-0173/24-00)