Allergen‐free extracts from birch, ragweed, and hazel pollen activate human and guinea‐pig submucous and spinal sensory neurons

Abstract

Background Non‐allergenic, low molecular weight components of pollen grains are suspected to trigger changes in gut functions, sometimes leading to inflammatory conditions. Based on extensive neuroimmune communication in the gut wall, we investigated the effects of aqueous pollen extracts (APE) on enteric and spinal sensory neurons. Methods Using Ca2+ and fast potentiometric imaging, we recorded the responses of guinea‐pig and human submucous and guinea‐pig dorsal root ganglion (DRG) neurons to microejection of low (<3 kDa) and high (≥3 kDa) molecular weight APEs of birch, ragweed, and hazel. Histamine was determined pharmacologically and by mass spectrometry (LC–MS/MS). Key Results Birch APE<3kDa evoked strong [Ca+2]i signals in the vast majority of guinea‐pig DRG neurons, and in guinea‐pig and human enteric neurons. The effect of birch APE≥3kDa was much weaker. Fast neuroimaging in human enteric neurons revealed an instantaneous spike discharge after microejection of birch, ragweed, and hazel APE<3kDa [median (interquartile range) at 7.0 Hz (6.2/9.8), 5.7 Hz (4.4/7.1), and 8.4 Hz (4.3/12.5), respectively]. The percentage of responding neurons per ganglion were similar [birch 40.0% (33.3/100.0), ragweed 50.8% (34.4/85.6), and hazel 83.3% (57.1/100.0)]. A mixture of histamine receptor (H1–H3) blockers significantly reduced nerve activation evoked by birch and ragweed APEs<3kDa, but was ineffective on hazel. Histamine concentrations in ragweed, birch and hazel APE's < 3 kDa were 0.764, 0.047, and 0.013 μM, respectively. Conclusions Allergen‐free APEs from birch, ragweed, and hazel evoked strong nerve activation. Altered nerve‐immune signaling as a result of severe pollen exposure could be a pathophysiological feature of allergic and non‐allergic gut inflammation.