Review of the Mechanisms of Snake Venom Induced Pain: It’s All about Location, Location, Location

Abstract

Pain—acute, chronic and debilitating—is the most feared neurotoxicity resulting from a survivable venomous snake bite. The purpose of this review is to present in a novel paradigm what we know about the molecular mechanisms responsible for pain after envenomation. Progressing from known pain modulating peptides and enzymes, to tissue level interactions with venom resulting in pain, to organ system level pain syndromes, to geographical level distribution of pain syndromes, the present work demonstrates that understanding the mechanisms responsible for pain is dependent on “location, location, location”. It is our hope that this work can serve to inspire the molecular and epidemiologic investigations needed to better understand the neurotoxic mechanisms responsible for these snake venom mediated diverse pain syndromes and ultimately lead to agent specific treatments beyond anti-venom alone.

Peripheral Nerve Block to Treat Pain Caused by Daboia palaestinae Envenomation

“…The exact mechanism of nerve injury causing pain and CRPS in snakebite victims remains unclear. 10 Routine analgesics were insufficient for this patient's pain relief. Although antivenom administration can alleviate pain in areas distant from the bite site by neutralizing circulating and locally presented venom compounds, tissue edema and ischemia around the bite site may hinder the delivery of antivenom to the envenomation strike point, 3 leading to continued pain.…”

“…Although antivenom administration can alleviate pain in areas distant from the bite site by neutralizing circulating and locally presented venom compounds, tissue edema and ischemia around the bite site may hinder the delivery of antivenom to the envenomation strike point, 3 leading to continued pain. 10 Therefore, it was decided to perform a regional nerve block with local anesthetics. As expected, this provided almost instantaneous pain relief.…”

“…A 2022 review of pain due to snakebite emphasized 3 aspects: molecular mechanisms of venom-induced pain, the anatomical site (local or remote), and the nature of venom-mediated pain, influenced by the snake’s evolutionary and geographic origin and venom proteome. 10 Conventional analgesics like paracetamol, nonsteroidal anti-inflammatory drugs, dipyrone, and opioids are effective for most snakebite cases. However, controlling the neuropathic pain caused by neurotoxins in the venom can be challenging, and it may lead to chronic conditions like complex regional pain syndrome (CRPS).…”

Characteristic Cases of Snake Bite in Sanjiwani Hospital

“…[10], [11], [13] In the literature, components of snake venom such as PLA2, a serine protease, and metalloproteinase caused an indirect effect that if lots of venoms were injected during the bite, it causes pain in the abdomen, then it triggers nausea-vomiting. [18] From the result, it is found that 8 (14,5%) of the sample present with bleeding. The study by Masroori and Cesaretli found that only (8,5%) and (28,5%) of the sample were present with bleeding.…”

Selective sensory nerve blocks for effective pain management in the emergency department for a term pregnant cobra snake envenomation patient

“…Acute localized moderate-to-severe pain is often documented as the first sign of a venomous snake bite (VSB). [ 2 , 3 ] The presynaptic and postsynaptic neurotoxins may directly interact with the nerve endings or indirectly cause severe pain secondary to ischemia due to local oedema. [ 1 ] Antivenom treatment fails to alleviate the local pain which may last for 48–72 h. [ 3 ] Weak opioids such as tramadol or paracetamol often provide inadequate analgesia.…”