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Evaluation of Adenosine, Lidocaine and Magnesium (ALM) treatment to enhance pain control and immune responses in a mouse model of hind paw injury
Author(s) -
RiveraLopez Leslie,
Chaplin Vanessa,
Pratt Gilbert,
Truong Thuyvi,
McNeal Neal
Publication year - 2021
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2021.35.s1.02577
Subject(s) - medicine , anesthesia , chronic pain , lidocaine , inflammation , hyperalgesia , nociception , physical therapy , receptor
Current mitigation strategies for orofacial pain in combat casualties rely predominantly on opioid and non‐steroidal anti‐inflammatory drugs, resulting in adverse effects such as nausea, apnea, and dependency. New effective pain control therapies are needed to support patient recovery, particularly in austere environments where access to medical care may be limited. Our study proposed that a combination of adenosine, lidocaine and magnesium (ALM), a recently developed drug for trauma, would significantly decrease pain responsiveness and inflammation in a mouse model of hind paw injury. Injury was induced by subcutaneously administering capsaicin or Complete Freund's Adjuvant (CFA) into the dorsal surface of the hind paw. Male SKH1‐Hrhr mice between the ages of 5‐ to 8‐weeks (n=95) were randomly assigned to three injury/assessment groups. The first group received a capsaicin‐induced injury to assess acute pain and inflammation in response to the injury. The second and third groups received CFA‐induced injury with 3‐hour and 24‐hour assessment, respectively, for chronic pain and inflammation response. Additionally, each group contained treatment subgroups of 10 animals each: (1) no injury (negative control); (2) injury only (positive control); (3) injury+lidocaine; and (4) injury+ALM. Pain assessment in the acute group was performed by behavioral observations. To evaluate changes in pain perception in the chronic pain response groups, we performed the von Frey behavioral test. Plasma was collected prior to euthanasia for cytokine multiplex analysis. Behavioral effects and multiplex analysis were analyzed by one‐way ANOVA with repeated measures and Tukey's post hoc comparison test. Data are represented as mean±SD with significance as alpha<0.05. Results showed that acute pain responses in the ALM+injury and lidocaine+injury groups were attenuated compared to the negative control group, with significantly decreased time spent in grooming (p<0.0001) and grooming events (p=0.0004 and p=0.0010), respectively. However, in the chronic pain response assessment at 3 and 24 hours, no significant differences were found within or between experimental groups. Immunoreactivity levels of the cytokines IL‐2, IL‐6, IFN‐γ and TNF‐α in the injury+ALM group, compared to positive and negative control groups, showed no statistically significant differences at any time point of the study. These findings suggest that injury interventions with ALM can decrease acute pain responsiveness but are ineffective at mitigating chronic pain and related immune responses.