DIET CAN EXERT BOTH ANALGESIC AND PRONOCICEPTIVE EFFECTS IN ACUTE AND CHRONIC PAIN MODELS A systematic Review of Preclinical Studies

Nutrition is an important component of well-being and accepted as a major modifiable determinant of non-communicable diseases. However, in human research, how nutrition and pain-generating- mechanisms interact with each other is not well understood. Preclinical animal research provides information to understand underlying physiologic and pathophysiologic mechanisms and to identify needs for human research. Thus, systematic review of preclinical animal research that investigate the interaction between nutrition and pain can contribute to identify underlying mechanisms of nutrition and pain and help us to identify needs for further human studies in this field.

To to give a systematic overview of the current evidence from preclinical animal studies regarding the analgesic and pronociceptive effects of various diets in non-neuropathic, non- cancer, or non-visceral acute and chronic pain models.

Protocol Registration
The review protocol was registered in the PROSPERO database (https://www.crd.york.ac.uk/prospero/) with the registration number (CRD42019133473).
Search Strategy and Eligibility Criteria
The search strategy was based on the Population, Exposure, Comparison, Outcome (PECO) framework (P= Animal Models; E= Nutrition; C=Non-comparison or Comparison; O= Pain – related outcome measures).
Inclusion Criteria;
- Studies conducted of animal models,
- Studies that investigate the association between acute or chronic non-neuropathic, non-visceral, nociceptive or inflammatory pain and nutrition,
- Studies that investigate diet and dietary factors, not mixed with any other treatment modalities,
- Studies written in English
Information Sources and Keywords
Two online databases were searched; PubMed and Web of Science by two reviewers (E.L. and A.Q.M.) independently up to (01/12/2020).
Three groups of keywords were combined: Animal models (population), nutrition (exposure) and Pain (outcome).
Study Selection
Study selection was performed by the same two, independent researchers (E.L. and A.Q.M.) based on two screening phases; firstly, titles and abstracts of the search results were checked. Secondly, full texts of possibly relevant articles were checked. Additionally, backward and forward tracking was performed.
Risk of Bias Assessment
The risk of bias assessment was performed using the Systematic Review Centre for Laboratory animal Experimentation (SYRCLE) tool. The quality of evidence was assessed with a modified “The Grading of Recommendations Assessment, Development and Evaluation” (GRADE) approach which can be used for systematic reviews of preclinical studies. The quality of evidence was assessed to investigate the transferability of the preclinical study findings to human research.

In animal models, excessive saturated, monounsaturated or omega-6 polyunsaturated fat ingestion and diets rich in fats and carbohydrates can decrease pain sensitivity in acute nociceptive pain, whereas it can induce mechanical allodynia and heat hyperalgesia in chronic inflammatory pain. Additionally, diets rich in anti-inflammatory ingredients such as omega-3 polyunsaturated fatty acids, curcumin, isoflavones, as well as a calorie-restricted diet can promote recovery from primary mechanical allodynia and heat hyperalgesia in chronic inflammatory pain. Additionally, this review suggests the transition of the preclinical studies that investigate the effects of high-fat diet, western diet, magnesium deficient diet, and high palatable diet on pain generating mechanisms to human subject research.