Abstract
Various types of pain were reported by people with Plasmodium falciparum and were mostly attributed to a symptom of malarial infection. Neural processes of pain sensation during malarial infection and their contributions to malaria-related death are poorly understood. Thus, these form the focus of this study. Swiss mice used for this study were randomly divided into two groups. Animals in the first group (Pb-infected group) were inoculated with Plasmodium berghei to induce malaria whilst the other group (intact group) was not infected. Formalin test was used to assess pain sensitivity in both groups and using various antagonists, the possible mechanism for deviation in pain sensitivity was probed. Also, plasma and brain samples collected from animals in both groups were subjected to biochemical and/or histological studies. The results showed that Pb-infected mice exhibited diminished pain-related behaviours to noxious chemical. The observed parasite-induced analgesia appeared to be synergistically mediated via µ-opioid, α2 and 5HT2A receptors. When varied drugs capable of decreasing pain threshold (pro-nociceptive drugs) were used, the survival rate was not significantly different in the Pb-infected mice. This showed little or no contribution of the pain processing system to malaria-related death. Also, using an anti-CD68 antibody, there was no immunopositive cell in the brain to attribute the observed effects to cerebral malaria. Although in the haematoxylin and eosin-stained tissues, there were mild morphological changes in the motor and anterior cingulate cortices. In conclusion, the pain symptom was remarkably decreased in the animal model for malaria, and thus, the model may not be appropriate for investigating malaria-linked pain as reported in humans. This is the first report showing that at a critical point, the malaria parasite caused pain-relieving effects in Swiss mice.
Highlights
The World Malaria Report 2018 estimated the global tally of new malaria cases and death as at 2016 to be 216 000 000 and 445 000, respectively (WHO 2018)
The present study established Plasmodium berghei (Pb)-induced analgesic-like effect in an animal model for malaria during life-threatening stage. This analgesic-like effect was enhanced with daily increase in parasitaemia level, and it was shown by a striking diminished pain-related behaviours
The effect seems to have central synergistic contributions of α2, μ-opioid and 5HT2A receptors. This assertion was drawn from the facts that when antagonists of α2, μ-opioid and 5HT2A receptor were used, there was increase in pain-related behaviours in the Pb-infected mice during the neurogenic and or inflammatory phase of formalin pain test compared to intact animals
Summary
The World Malaria Report 2018 estimated the global tally of new malaria cases and death as at 2016 to be 216 000 000 and 445 000, respectively (WHO 2018). In the infection inflammationinduced pain pathway, pathogens and their products are known to have prototypic molecular pattern that stimulate Toll-like receptor which in turn activate biosynthesis and release of proinflammatory cytokines (Miller et al 2009; Schedlowski, Engler & Grigoleit 2014). Peripheral nociceptor terminals via their receptors and ion channels are sensitised by these mediators, resulting in increasing pain sensation (Pinho-ribeiro et al 2017). This pathway was believed for years as the sole genesis of pain during infection, emerging studies, showed a direct pathogen-induced pain at a specific density in parasitaemic infection
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