Analgesic effects of dietary caloric restriction in adult mice

Abstract

Nociception was studied in male mice, mostly of the C57BL/6 strain, during continuous or prolonged restriction of caloric intake (60% of ad-libitum) from midlife to senescence (up to 105 weeks). Restricted mice showed fewer licking or biting responses 20-60 min after hind paw injection of 5% formalin at 46 and 70 weeks, but not at 93 weeks. Also, they showed longer response latencies around 46 weeks of age in the 52 degrees C hot-plate test, which partial tail amputation failed to affect, although it did produce at least 2 weeks of chronic neuropathic hypersensitivity in ad libitum controls. Injection of collagen subcutaneously at 36-42 weeks led to chronic hyperalgesia in the DBA/1 but not the C57BL/6 strain, measured weekly by the barely nociceptive 50 degrees C hot-plate test to minimize damage. This collagen-induced arthritic hyperalgesia was then gradually and reversibly blocked during 9-15 weeks of caloric restriction starting at 53-58 weeks. In longitudinal trials on normal mice, performed every 2-4 weeks between 42 and 105 weeks with the 50 degrees C hot-plate, caloric restriction led to altered latencies (higher relative to controls) only in the last 10-20 weeks, perhaps because it delayed the onset of age-related peripheral neuropathies. In conclusion, long-term caloric restriction leads to significant hypoalgesia in pre-senescent mice subjected to above-threshold pain of widely different durations, the effect disappearing at later ages unless spontaneous neuropathies become influential. A reduction in cumulative food intake thus appears to generate antinociceptive signals in adult male mice, perhaps serving specifically to promote riskier behavior during prolonged food shortages.

Fasting Therapy for Treating and Preventing Disease - Current State of Evidence

“…The analgesic and antinociceptive effects of caloric restriction have been confirmed experimentally [88], and reduced responses to experimental pain have been associated with changes in endogenous opioid system [89]. So far, mostly smaller or nonrandomized studies have investigated the effect of fasting on chronic pain.…”

Laboratory environmental factors and pain behavior: the relevance of unknown unknowns to reproducibility and translation

“…Failure to provide bedding material for a rat to make a nest for her pups can lead to hyperalgesia in those pups when they become adults 55,56 , and the handling of young animals (for example, related to injections, and involving the stress of maternal separation) can cause long-term alterations in pain sensitivity 41,[57][58][59][60][61][62][63] . A growing literature also documents the effect of diet on pain sensitivity [64][65][66][67][68][69][70][71][72][73][74][75][76][77][78][79][80] . In one case, differences in the soy content of rat chow turned out to be wholly responsible for a failure to replicate in Baltimore the findings of studies originally performed in Jerusalem 65 .…”

Depressed Immune Responses and Accelerated Splenic Apoptosis due to Experience of Food Deprivation and Inequality but not Unstable Social Status in Balb/c Mice

“…Control Group: this group had free access to food without any deprivation or inequality 2. Food Deprivation (See) Group (FD + See): each mouse in this group received one-third (1.5 g/day) of their normal daily food intake between 09: 00 and 11: 00 a.m., and experienced food in- It should be noted that food deprivation induces states distinct from the physiological situation of caloric restriction [25]. Moreover, we used only male animals, in order to avoid the variation attributed to gender and sex differences [26].…”