Biomedical Engineering Reference
In-Depth Information
sensory fibers were detected in the periosteum, bone marrow cavity, and vascular
canals in long bones of mature and developing animals.
The blood vessels in the bone marrow are abundantly innervated, through both
sympathetic and afferent nerve fibers. Afferent nerve fibers are also connected
with receptors imbedded in the parenchyma of marrow [121]. In Figure 1.18, an
example of the innervations is given.
Growth-associated protein (GAP-43) is expressed in conditions of embryonic
growth, during axonal regeneration, and even at maturity in certain areas of
the brain known to exhibit synaptic plasticity. Protein gene product (PGP) 9.5
is a cytoplasmic protein specific for neurites, neurons, and cells of the diffuse
neuroendocrine system. GAP-43 and PGP 9.5 are often used as neuronal markers,
cf. [122].
In the field of neuroscience, tachykinin peptides are one of the largest families of
neuropeptides, found from amphibians to mammals. They are named so because
of their ability to rapidly induce contraction of gut tissue. Tachykinins are widely
distributed in the body and function as neurotransmitters and neuromodulators.
Five tachykinin subtypes: substance P (SP), neurokinin A, neurokinin B, neuropep-
tide K, and neuropeptide Y; and three receptor subtypes: neurokinin-1, -2, and -3
receptors, have been identified. SP was the first peptide of the tachykinin family
to be identified. It is considered to be an important neuropeptide, and to function
in the nervous system and intestine. However, recent studies in the analysis of
SP receptors, particularly neurokinin-1 receptors (NK
1
-Rs) that have high affinity
for SP, have demonstrated that NK
1
-Rs are distributed not only in neurons and
immune cells but also in other peripheral cells, including bone cells [123]. The
distribution of tachykinin-immunoreactive axons and neurokinin receptors sug-
gests that tachykinins may directly modulate bone metabolism through neurokinin
receptors, cf. survey paper on the bone innervations by Goto [124], and also [125].
SP is an undecapeptide with multiple effects on the cardiovascular, gastrointesti-
nal, and urinary systems as well as complex central nervous system functions such
as learning and memory. SP is released from the terminals of specific sensory
nerves; it is found in the brain and spinal cord, and is associated with inflammatory
processes and pain [126, 127].
1.3.3.1
Anatomy of Bone Innervation
An extensive plexus of nerve fibers investing the periosteum and joints gives bone
the lowest pain threshold of any of the deep tissues. A-delta (small myelinated)
fibers and C (small unmyelinated) fibers contain deep somatic nociceptors with
free nerve endings. Deep somatic pain is usually described more as aching than
sharp, and is less well localized than cutaneous somatic pain. In the human femur,
all cortical Volkmann's and Haversian canals contain unmyelinated fibers, and
some contain both myelinated and unmyelinated fibers. SP, which mediates pain
sensation, is attached to these fibers.
In rat and dog models, nerves in bone marrow have been found to be associated
with venous sinuses. These are single fiber nerves, independent of the blood
