Probiotics In Pain Relief: A Mini Review

Pain is a vital function of the nervous system that provides the body with a warning of potential or actual injury (Michel et al. ,2003). Specialized sensory receptors responsible for the detection of noxious stimuli called nociceptorsare involved in transforming these stimuli into electric signals for conductionto the central nervous system (Kidd and Urban 2001)Inflammatory response accompany the development and persistence of pain (White et al. , 2005; Watkins et al. ,2003); it is characterized by redness, swelling, pain, heat andloss of function. The formation of prostalgladin from Arachidonic acid is initiated and catalyzed by cyclooxygenase (COX). Prostaglandins activate and sensitize nociceptors or act by stimulating other pain receptors to produce pain producing substance; Pain mediators such as cytokines and bradykins released by damaged tissuesinduces cyclooxygenase andstimulates the release of prostalgladin and these mediators may also directly sensitize nociceptors (Sinatra and Bigham 1997)

MECHANISM OF PAIN RELIEF

Pain mediators activates and sensitize nociceptors (White et al. , 2005). Nonsteroidal anti-inflammatory drugs (NSAIDs) are used in the treatment of pain and inflammation by inhibiting the enzyme COX which occur in two isoforms COX-1 and COX-2; these NSAIDs reduce the production of prostaglandins, thus reducing the sensitization of nociceptors and the overall effect of inflammatory pain (Burmester et al. , 2011; Hochberg et al., 2012; Arakawa et al. , 2009). A number of side effects are associated with the use of NSAIDs and these include: Gastrointestinal complications, increase risk of renal disease and cardiovascular diseases; these has led to the search for other pain reliefs with little or no adverse effects. The damaging effect seen in the use of NSAID is observed in the pain cascade initiated by COX-1. . The understanding of pain mechanism has led to the discovery of COX-2 selective inhibitors (coxibs) which have an ameliorating effect. It was thought that targeting COX-2 enzyme would circumvent the adverse effect seen in the use of NSAID which target both COX-1 and COX-2. Recent studies have however shown that coxibs also contribute to cardiovascular risk, may induce disturbance in renal function (Arome et al. , 2016; Puja and Justin 2010).

A need for an alternativetherapy that is not only safe but has a low risk profile is thus needed. From our search probiotics came out handy as a form of nutraceutical in the treatment of pain PROBIOTICS Probiotics are live organism that confers health benefit on its host when administered in sufficient amounts (FAO 2001). The intestinal microbiota is dominated by species of Lactobacillus and Bifidobacteria (Llamas-Arriba) and these constitute major probiotics (Guarner, 2003); also included are species of the yeast genus Saccharomyces; others are genus of Streptococcus, Enterococcus, and Bacillus. Some clinical trials and genomic toolshave been carried out to determine the appropriate strains of these genus that can be effectively applied; cocktails of differentstrains has also been produced to better utilize the combined benefits of identified strains. Examples of some probiotics include E. coli NissLE, Lactobacillus rhamnosus, GG, L. acidophilus and L. delbrueckii, DR10 and DR20 by Fonterra, VSL#3??? Evidence has risen in support of the use of probiotics in the treatment and prevention of some pathologies including diabeties (Nuñez,2018). These benefit are strain specific (Vilaseca, 2018), in that the same species may not impute same effect, these benefits have also heralded their being used in the development of functional foods and as therapeutics (Dekker, 2007; Madiedo, 2018)Strict criteria’s must be met before a strain is administered as a probiotics, and these includes ability of being non pathogenic and toxic, ability to resist the acid in the stomach and bile, capacity to adhere to the intestinal epithelium (Crowley, 2013; Joint FAO/WHO Working Group, 2002). Bacteremia, sepsis, antimicrobial resistance and general effect on host immune system are areasof concern in the use of probiotics, however, studies have revealed that the use of probiotics is generally safe but caution should be taken in immunocompromised and severally ill patients (Hojsak, 2013)

II. APPLICATION OF PROBIOTICS

Probiotics have been applied to treat and curb the effect of some diseases and ailments, some beneficial effects have been observed with its use and theirapplications have yielded beneficial effects. Bottle fed infants are not as healthy as breast fed ones and infectious rate is high in the former, probiotics have been incorporated in infant formulae to mimic the microbiota profile of breast-fedinfants, the prevention andtreatment of diarrhea in children and reduction of theinfection of the upper respiratory tract (Moreno, 2018; Pigneur,2013; Gibson and Rastall 2004). Antibiotic resistance to antimicrobials have been found to increase with the use of antibiotics overtime. An alternate method to reduce these resistance has been implied in the use of probiotics (Abuja and Julián 2018). Prevention of pouchitisand treatment of its chronic forms (Jonkers et al 2012) has been achievedwith VSL#3. Its promising effect has been seen in ulcerative colitis, inflammatory bowel disease such as constipation, crohns disease, pouchitis, Helicobacter pylori infection, irritable bowelsyndrome, Antibiotic-Associated Diarrhoea and C. difficile -Induced Diarrhoea, (Dimidi, 2017)

III. MECHANISM OF ACTION OF PROBIOTICS

The mechanism of action may not have been fully elucidated but some have been proposed as being possible ways in which they act. Theses mechanisms include: strengthening of the intestinal barrier, antagonistic effect on pathogenic microbes, elimination of other microbes through competitive exclusion and increase rate of adhesion to epithelia cell surface.

Antagonistic effect on pathogenic microbes is another mechanism that has been proposed for the action of probiotics. Antimicrobial effect on pathogenic bacteria through the production of antibacterial substance such as bacteriocins, lactic acid, hydrogen peroxide and conjugated bile acid (De Keersmaecker et al. ,2006). Studies byGoudarzi et al. , 2014 and rettger 1905 reveals thatthe ability to produce proteolytic enzymes which dissolve digest approaching bacteria may be the reason forantipathogenic property observed in them. shows that certain probiotics microbesproduce proteolytic enzymes that dissolve and digest approaching bacteria. Theyhave also been found to possessantifungal (Dal Bello et al. ,2007); studies have also shown that viral particles can be inactivated by probiotic substance, lactobacillus rhamnosus GR-1 and L. fermentum RC-14 inactivated adenovirus by studies carried out by Cadieux et al. (2002); animal studies has indicated a great reduction of poliovirus infection by the marine bacterium Moraxella sp(Girones et al. ,1989). C. Probiotics may also eliminate the colonization and proliferation of other microbes through competitive exclusion. Several means have been used by probiotics to prevent colonization of the GIT. One of such means is the competition for essential nutrient like iron. Unlike other bacteria, Lactobacilli do not need iron (Weinberg, 1997) and could make it unavailable to other pathogenic microbes. other anti-adhesive properties thought to be exhibited by probiotics through competitive exclusion include increased expression of the mucin gene, binding rapidly to mucin and colonic cell lines and completion for receptor sites. Mack et al. (1999) in their investigation showed the inhibiton of the adhelsion of enteropathogenic Escherichia coli 0157H7 to HT-29 cells by Lactobacillus GG and Lactobacillus plantarum 299 V through the competition for receptor site and increased stimulation of the production ofmucin

PROBIOTICS IN PAIN RELIEF

Efficient painmanagement remains a considerable challenge in health care and basic research (Lapointe, 2011). Probiotics have been shown to be able to regulate COX II in studies carried out by otte et al. (2009) whichreveals that specific probiotic strains can be considered as therapeutic alternative in the regulation and expression of COX II in the intestinal epithelium to curb its inflammatory effect. This ability can be channeled in pain relief by expounding the mechanism and pathways involved and applying to other where there is need to regulate COX II expression. Pathological pain is triggered by proinflammatory cytokines such as IL-1β, IL-6, and TNF-α (Zhang and An 2007), it therefore follows that pain can be reduced and possibly prevented if the production ofthese cytokines are regulated and inhibited respectively and this has been confirmed by studies carried out by Hart et al. (2004); in their investigationit wasrevealed that some probiotic bacteria inhibited the production of proinflamatory cytokines. Furthermore, pain, if not controlled adequately during immediate postoperative periods may lead to greater pain during recovery thus, optimal analgesic therapyshould not lead to the development of chronic pain and must have minimal or no side effect (Lee et al. , 2005).

Studies carried out by Calabuig et al. (2018) revealsthatafter third molar extraction, oral probiotics helped achieve a larger reduction in pain towards the end of the first week. This also reveals the ability of probiotics strain to reduce pain, It thus follows that some strainsmay have promising effect in pain reduction. Studies on Irritable bowel syndrome (IBS) has shown that IBS is characterized by abdominal pain and/or discomfort related to abnormal bowel habits (Thompson et al. ,1999). some clinical trials have indicated that in the treatment of IBS by probiotics, associated symptoms such as pain were also relieved; one of such is Vilaseca. (2018) who concludedthatthe probiotic mixture testedcould relieve effectively acute diarrhea and associated symptoms: pain being one of such associated symptoms mentioned in the work, when astudy on the beneficial effect of a probiotics mixture in adult patients with acute diarrhea was carried out. A table from Gabriela et al. 2005 titled ‘Most representative studies of probiotic uses in different GI diseases’ revealed studies by other researchers, where some probiotic strains have significantly improved pathologic pain.