Electrophysiological and Structural Aspects in the Frontal Cortex After the Bee (Apis mellifera) Venom Experimental Treatment

Abstract

The aim of this study is to evaluate the bioelectrical and structural-functional changes in frontal cortex after the bee venom (BV) experimental treatments simulating both an acute envenomation and a subchronic BV therapy. Wistar rats were subcutaneously injected once with three different BV doses: 700 μg/kg (T(1) group), 2100 μg/kg (T(3) group), and 62 mg/kg (sublethal dose-in T(SL) group), and repeated for 30 days with the lowest dose (700 μg/kg-in T(S) group). BV effects were assessed by electrophysiological, histological, histochemical, and ultrastructural methods. Single BV doses produced discharges of negative and biphasic sharp waves, and epileptiform spike-wave complexes. The increasing frequency of these elements suggested a dose-dependent neuronal hyperexcitation or irritation. As compared to the lower doses, the sublethal dose was responsible for a pronounced toxic effect, confirmed by ultrastructural data in both neurons and glial cells that underwent extensive, irreversible changes, triggering the cellular death. Subchronic BV treatment in T(S) group resulted in a slower frequency and increased amplitude of cortical activity suggesting neuronal loss. However, neurons were still stimulated by the last BV dose. Structural-functional data showed a reduced cellular density in frontal cortex of animals in this group, while the remaining neurons displayed both specific (stimulation of neuronal activity) and unspecific modifications (moderate alterations to necrotic phenomena). Molecular mechanisms involved in BV interactions with the nervous tissue are also discussed. We consider all these data very important for clinicians who manage patients with multiple bee stings, or who intend to set an appropriate BV therapy.

Mass envenomation of a mare and foal by bees

“…Additional pain control in severely stung human patients has been achieved with opioids, which are useful for both nociceptive and inflammatory pain, but not neuropathic pain. 8,27 In the present case, morphine administered IV on a single occasion seemed to provide additional analgesia to that of detomidine alone. A continuous rate infusion of morphine, in combination with detomidine and possibly with ketamine, would have been used had there been no constraints on treatment.…”

“…With knowledge of the effects of venom constituents, multimodal analgesic treatment would seem logical. In mass envenomation, there are likely to be components of nociceptive, inflammatory and neuropathic pain . Peripheral inflammatory pain is likely secondary to tissue necrosis (particularly of muscle, skin and possibly intestine), histamines and inflammatory cytokine release caused by venom components.…”

“…It is rational to use NSAIDs and corticosteroids for the inflammatory pain component in bee stings. Additional pain control in severely stung human patients has been achieved with opioids, which are useful for both nociceptive and inflammatory pain, but not neuropathic pain . In the present case, morphine administered IV on a single occasion seemed to provide additional analgesia to that of detomidine alone.…”

“…In mass envenomation, there are likely to be components of nociceptive, inflammatory and neuropathic pain. 27 Peripheral inflammatory pain is likely secondary to tissue necrosis (particularly of muscle, skin and possibly intestine), histamines and inflammatory cytokine release caused by venom components. Neuropathic pain is likely a direct effect of venom on nerve tissue.…”

Bee (Apis mellifera) Venom Produced Toxic Effects of Higher Amplitude in Rat Thoracic Aorta than in Skeletal Muscle—An Ultrastructural Study

“…Pure, dry BV was used in this study. The venom was collected from ten hives in an apiary of a local race of European honeybees ( Apis mellifera carpatica ) as previously described (Florea & Crăciun, 2011; Florea et al, 2011). The crystallized BV was reconstituted in 150 mM NaCl, 5.5 mM glucose, and 5 mM HEPES [4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid] at pH 7.4 in order to obtain injectable aqueous solutions.…”