Page 28 - CASA Bulletin of Anesthesiologisy 2022 9(6)-1 (3)

CASA Bulletin of Anesthesiology

( ) w A ’
antinociceptive effect is primarily mediated by regulation of calcium channels that are involved
in central sensitization and pain hypersensitivity. The NMDA receptor regulates flux of ions such
as sodium, calcium and potassium. Inhibition of NMDA receptors by Mg will prevent calcium
entering the cell which is often the first step required to initiate and maintain central
sensitization. Mg therapy has also shown to be beneficial in treating neuropathic pain, which is a

result of peripheral or central sensitization. Mg is also involved in a variety of enzymatic
reactions and synthesis of proteins responsible for neuronal function and survival. It promotes
axonal growth, neural cell proliferation and repair following neural damage 40, 41 . Mg can provide
‘ ’ U ,
levels decrease calcium influx through NMDA receptors will increase, causing cells to swell and
undergo apoptosis. This leads to degeneration of uninjured nearby nerves as well. Mg can block
NMDA receptors and the neurotoxic effects of calcium . Major surgeries such as complex spine
42
surgeries cause extensive surgical tissue and surrounding nerve injuries – Intravenous Mg can be
helpful for perioperative pain caused by the combination of intraoperative neural injuries and
pre-existing neuropathic pain. Intravenous Mg has shown to decrease postoperative opioid
consumption and postoperative pain scores both at rest and at movement. In a study by Jabbour
et al., patients who received both magnesium and ketamine infusions demonstrated lower
cumulative morphine consumption up to 48 hour postoperatively when compared to patients who
only received a ketamine infusion. Although magnesium is not currently widely utilized for
postoperative pain, it shows great potential as an adjunct to reduce acute postoperative pain 43, 44 .
Gabapentinoids

Gabapentin was initially developed to treat epilepsy and developed to primarily modulate
GABA metabolism. However, instead, they were found to inhibit the 21 subunits of voltage
gated calcium channels which are abundant in the cerebellum and hippocampus and can
attenuate neurotransmission. Through this mechanism, it was hypothesized that gabapentinoids
could be used to control pain by reducing neuronal hyperexcitability. Gabapentinoids have
successfully demonstrated its ability to treat pain and has been widely used to treat a variety of
neuropathic pain conditions including painful diabetic neuropathy, post-herpetic neuralgia and
45
neuropathic pain from traumatic spinal cord injuries. Due to its efficacy in treating chronic pain
conditions, gabapentinoids have also been widely used in the perioperative period and
considered essential components of protocols for early recovery after surgery and multimodal
analgesia including complex spine surgeries. A meta-analysis study of 281 randomized clinical
trials that compared gabapentinoids to placebos and other analgesic regimens concluded that
there was no statistically significant difference in acute, subacute, or chronic pain and opioid
sparing effect. On the other hand, gabapentinoids were associated with less postoperative nausea
and vomiting but had other side effects such as dizziness and visual disturbances 46, 47 . These side
effects are primarily due to the effect of gabapentinoids on the cerebellum & hippocampus where
21 voltage gated calcium channel is richly expressed. Other side effects include balance
disorders (ie ataxia), sedation, somnolence and cognitive impairment. Pregabalin was associated
with a three times higher risk of serious adverse events (ie. life threatening events resulting in
death, disability, or significant loss of function or causing hospital admission or prolonged
hospitalization) .
48

P a g e 28 | 75