Neutrophil infiltration is implicated in the sustained thermal hyperalgesic response evoked by allergen provocation in actively sensitized rats

Abstract

It has been proposed that allergen provocation induces hyperalgesia but the involvement of immunoglobulin E and leukocytes remains poorly understood. Here, we have compared the profile of allergen-evoked thermal hyperalgesic response in both passively and actively sensitized rats, and investigated the role of leukocytes in allergen-evoked nociception. Wistar rats were passively sensitized with an intraplantar injection of immunoglobulin E anti-dinitrophenylated bovine serum albumin monoclonal antibody (0.5 microg/paw), and challenged with dinitrophenylated bovine serum albumin (0.5 microg/paw) 24 h later. Alternatively, the animals were actively sensitized with a mixture of Al(OH)3 and ovalbumin and challenged intraplantarly with ovalbumin (12 microg/paw) 14 days later. We found that the thermal hyperalgesic responses set in very rapidly and with comparable intensity in both passively and actively sensitized rats. However, while in the former group the response was shorter, peaking within 1 h and reducing thereafter, a marked plateau was observed from 1 to 6 h post-challenge in the latter group. Actively sensitized rats also had higher neutrophil influx in the plantar tissue, as attested by both myeloperoxidase activity and histological analysis. Treatment of actively sensitized rats with either fucoidin (10 mg/kg, i.v) or anti-rat neutrophil antiserum (i.p.) reduced neutrophil accumulation and the late hyperalgesic response noted from 3 to 6 h post-challenge. Thus, we conclude that though immunoglobulin E-mediated mechanisms can cause thermal hyperalgesia, components of the cellular immune reaction are crucial in order to amplify and sustain the immediate hyperalgesic response triggered by allergen, in a process dependent on neutrophil recruitment.

Measuring Changes in Tactile Sensitivity in the Hind Paw of Mice Using an Electronic von Frey Apparatus

“…Neutrophils were counted in 3 hind paws per treatment from the heel to the toes in adjacent fields of view at 400X magnification (A). Mast cells were counted in 3 footpads/treatment and their degranulation status was scored based on the number of visible granules outside of the cell boundary: intact (0), mild (0-10), moderate (10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20), extensive (21+), as described previously 10 (B). To avoid counting the same cells twice, the investigators assessing neutrophil numbers and mast cell degranulation levels in the hind paw sections used a grid inscribed in the eyepiece reticle.…”

CD11b+Ly6G−myeloid cells mediate mechanical inflammatory pain hypersensitivity

“…Neutrophils secrete many proinflammatory mediators but also produce opioid peptides that might reduce pain. This dichotomy is evident in the literature, with studies showing that these cells can increase (53)(54)(55) or decrease (56, 57) hypersensitivity, whereas others have shown no effect (58,59) in various models of inflammatory pain. Our results suggest a lack of any major contribution for these cells to pain, at least under our conditions and in other models in which clear depletion was demonstrated.…”

Resident microglia die and infiltrated neutrophils and monocytes become major inflammatory cells in lipopolysaccharide‐injected brain

“…However, MPO immunoreactivity was neither detected in ramified CD11b 1 cells in the contralateral side (Fig. 4A, upper panel) (Lavich et al, 2006) (Fig. 4B).…”