Evidence for the modulation of nociception in mice by central mast cells

Abstract

Background Hyperalgesia that develops following nerve ligation corresponds temporally and in magnitude with the number of thalamic mast cells located contralateral to the ligature. We tested the possibility that mast cells modulate nociception centrally, similar to their role in the periphery. Methods We examined the central effect of two hyperalgesic compounds that also induce mast cell degranulation and stabilized mast cells using cromolyn. Results Thermal hyperalgesia (tail flick) induced by nerve growth factor (NGF, a neurotrophic compound) and mechanical hyperalgesia (von Frey) induced by dynorphin A (1–17) (opioid compound) each correlated with the percent of thalamic mast cells that were degranulated. Degranulation of these mast cells by the central injection of compound 48/80, devoid of neurotrophic or opioid activity, was sufficient to recapitulate thermal hyperalgesia. Stabilization of mast cells by central injections of cromolyn produced no analgesic effect on baseline tail flick or von Frey fiber sensitivity, but inhibited thermal hyperalgesia produced by compound 48/80 and tactile hyperalgesia induced by dynorphin and by Freund’s complete adjuvant. Finally, chemical nociception produced by the direct activation of nociceptors by formalin (phase I) was not inhibited by centrally injected cromolyn whereas chemical nociception dependent on central sensitization (formalin-phase II and acetic acid-induced abdominal stretches) was. Conclusions These convergent lines of evidence suggest that degranulation of centrally located mast cells sensitizes central nociceptive pathways leading to hyperalgesia and tonic chemical sensitivity.

Mast cell‐neural interactions contribute to pain and itch

“…Almost 50% of histamine and 25% of TNF‐α are attributed to mast cells in the rat brain . Mast cell activation may therefore contribute to nociception via direct central interactions in the brain as demonstrated recently in a spinal nerve ligation model in mice . This study also demonstrated that nerve growth factor (NGF), formalin, and dynorphin‐induced hyperalgesia involved degranulation of mast cells in the brain of mice.…”

“…26,53 Mast cell activation may therefore contribute to nociception via direct central interactions in the brain as demonstrated recently in a spinal nerve ligation model in mice. 44 This study also demonstrated that nerve growth factor (NGF), formalin, and dynorphin-induced hyperalgesia involved degranulation of mast cells in the brain of mice. It is likely that mast cells in the CNS are a critical player in the multicellular repertoire orchestrating central sensitization.…”

“…Brain neuroimaging also demonstrated the existence of central sensitization in patients with SCD . Mast cells are also present in the meninges and different regions of the brain including thalamus and are known to influence blood‐brain barrier permeability . Their number and distribution in the brain are affected by the environment, age, gender, pathological condition, and stimuli such as stress .…”

“…41,43 Mast cells are also present in the meninges and different regions of the brain including thalamus and are known to influence blood-brain barrier permeability. 26,[44][45][46] Their number and distribution in the brain are affected by the environment, age, gender, pathological condition, and stimuli such as stress. 26,27,[47][48][49][50] In the brain, mast cells may directly interact with the nociceptive neurons depending upon their location and proximity to nociceptive pathways and/or via their bidirectional interactions with microglial/astroglial cells.…”

T Cell Subpopulations in the Physiopathology of Fibromyalgia: Evidence and Perspectives

“…Pain in fibromyalgia involves neuroinflammatory processes triggered by mast cells and microglia [31][32][33][34][35]. Mounting evidence indeed supports the role of mast cells in fibromyalgia comorbid disorders and painful conditions [6,36,37].…”