3.3 Neuroplastic effects
In addition to affecting the sensory and inflammatory aspects of pain,
psychedelics may also influence chronic pain through their ability to
promote neuroplasticity.25 Neuroplasticity is the
brain’s ability to reorganize neural pathways and forge new
connections.39 Neuroimaging studies have revealed that
chronic pain conditions such as chronic low back pain, complex regional
pain syndrome, and osteoarthritis are all associated with altered
functional connectivity between spatially distinct brain
regions.40-43 For example, functional MRI (fMRI)
studies have demonstrated that chronic low back pain is associated with
a reorganization of functional connectivity between sensory, cognitive,
and limbic areas (e.g., nucleus accumbens and the prefrontal
cortex [PFC]). It is also associated with a disruption of the
default mode network (DMN) — a system of connected brain areas that
show increased activity when the individual is passively resting and
mind-wandering. These connectivity changes likely reflect maladaptive
plasticity and reorganization of functional brain circuits due to
persistent pain signaling.40,41 By stimulating neural
plasticity and regrowth of connections between brain
cells,44 psychedelics could potentially counteract
these observed connectivity alterations and remodel the disrupted
networks involved in pain. As a result, psychedelics could temporarily
disrupt these patterns of brain activity, providing a window for
rewiring neural connections and restoring more optimal network
functioning. This could potentially disentangle the clustering of
sensory, cognitive, and affective components of pain, enabling a
transformed understanding of the pain experience.
Relatedly, these compounds have been theorized to be linked with changes
in entropy and complexity in brain dynamics,45,46leading to changes that may be helpful in breaking out of rigid
cognitive and behavioral patterns. By disrupting these patterns,
psychedelics may facilitate the adoption of more adaptive pain-related
beliefs, thought processes, and actions.