Spinal injection of IL-2 or IL-15 alters mechanical and thermal withdrawal thresholds in rats

Abstract

IL-2 and IL-15 were tested for effects on responses to mechanical or thermal stimuli when spinally administered to male Sprague-Dawley rats with surgically implanted intrathecal catheters. Restricted doses of both IL-2 and IL-15 produced increased responsiveness to mechanical stimulation of the hindpaws. This effect lasted up to 48 hours. IL-2 had biphasic effects on thermal responses whereas IL-15 produced thermal hypalgesia alone. These effects dissipated within 24 hours. These results suggest that IL-2 and IL-15 may participate in the generation of hyperalgesia in some pain conditions.

Biological phenotypes underpin the physio‐somatic symptoms of somatization, depression, and chronic fatigue syndrome

“…In the mouse, intraperitoneal administration of IL-2 enhances the amnesic effects of scopolamine (76). In rats, spinal IL-2 injections enhance hindpaw responses, with biphasic effects on thermal responses, indicating that IL-2 modulates hyperalgesia (77). Plasma IFNc and IFNc-induced pathways are associated with hyperalgesia and chronic fatigue following Epstein-Barr virus and Parvovirus B19 infection (78,79).…”

Osteoarthritis joint pain: The cytokine connection

“…Intraplantar administration of IL-2 in the naïve hindpaw [38] and intrathecal injection post nerve injury [39] increased the time until paw withdrawal upon application of radiant heat. On the other hand, a different series of studies showed a dose-dependent effect of intrathecal IL-2 in naïve rats: a low dose increased heat sensitivity, while a higher dose decreased sensitivity [40]. In addition, the lower dose of IL-2 increased mechanical sensitivity, while the higher dose had no effect [40].…”

“…On the other hand, a different series of studies showed a dose-dependent effect of intrathecal IL-2 in naïve rats: a low dose increased heat sensitivity, while a higher dose decreased sensitivity [40]. In addition, the lower dose of IL-2 increased mechanical sensitivity, while the higher dose had no effect [40]. IL-15 has been proposed as a pro-inflammatory cytokine that supports immune infiltration, with possible implications in the development of pain [41].…”

“…IL-15 and its receptor have been located on astrocytes and microglia in the spinal cord, and intrathecal injection of an IL-15 antibody prevented macrophage and T-cell recruitment into the sciatic nerve after nerve injury [42]. Intrathecal injection of IL-15 into naïve rats also induced mechanical and thermal sensitivity [40]. …”

Evaluation of serum cytokines in cats with and without degenerative joint disease and associated pain

“…Il-2 and IL-8 have been less consistently associated with pain, though each has been investigated in experimental or chronic pain conditions. IL-2 has been demonstrated to have both hyperalgesic and analgesic properties in rodent models, dependent on location and route of administration (Song et al, 2002; Cata et al, 2008). In one study, the concentration of IL-8 was found to be higher in plasma samples from OA patients than controls (Mabey et al, 2014), and another study found higher levels of IL-8 mRNA expression from synovial biopsies in OA patients than patients with meniscal tears (Nair et al, 2015), but other studies have failed to show a strong relationship between IL-8 and pain.…”