Добавил:
Sekretar
kiopkiopkiop18@yandex.ru
t.me/Prokururor I Вовсе не секретарь, но почту проверяю
Опубликованный материал нарушает ваши авторские права? Сообщите нам.
Вуз:
Предмет:
Файл:Ординатура / Хирургия / @xirurgi_2025 / @xirurgi_2025 - 597 - файл
.pdf
192
https://t.me/med1917
Important to Know
Graft take and hair regrowth might be
impaired in scarred areas.
Postoperative Care
Achieving the optimal result after scar revision
surgery always includes proper postoperative
care such as wearing compression garments with
or without additional silicone scar pads, using
UV/sun protection, and adding additional nonsurgical applications (e.g., lasers when appropriate; see respective chapters).
Conclusion
Surgical scar therapy includes a multitude of different techniques from microsurgical to local
aps, from dermabrasion to serial excisions, from
lipolling or skin grafts to hair transplantation.
Not all techniques are suitable for every type of
scar. Minimal new scarring and preventing problematic scars from the start should be standard in
every surgical procedure. Before any intervention, however, thorough consultation of the
patients’ wishes is required to align expectations
with possibilities.
References
1. De Filippo RE, Atala A. Stretch and growth: the
molecular and physiologic inuences of tissue expansion. Plast Reconstr Surg. 2002;109(7):2450–62.
2. Karimi H, Lati NA, Momeni M, Sedigh-Marou S,
Karimi AM, Akhoondinasab MR. Tissue expanders;
review of indications, results and outcome during 15
years’ experience. Burns. 2019;45(4):990–1004.
3. Dong C, Zhu M, Huang L, Liu W, Liu H, Jiang K,
etal. Risk factors for tissue expander infection in scar
reconstruction: a retrospective cohort study of 2374
consecutive cases. Burns Trauma. 2020;8:tkaa037.
4. Smolle C, Tuca A, Wurzer P, Spendel SM, Forbes AA,
Spendel S, etal. Complications in tissue expansion:
a logistic regression analysis for risk factors. Burns.
2017;43(6):1195–202.
5. Shin H, Shin J, Lee JY. Scarred scalp reconstruction
with a rectangular expander. Arch Craniofac Surg.
2020;21(3):184–7.
E. Koellensperger and G. Germann
6. Goutos I, Yousif AH, Ogawa R.W-plasty in scar revision: geometrical considerations and suggestions for
site-specic design modications. Plast Reconstr
Surg Glob Open. 2019;7(4):e2179.
7. Kadakia S, Ducic Y, Jategaonkar A, Chan D. Scar
revision: surgical and nonsurgical options. Facial
Plast Surg. 2017;33(6):621–6.
8. Sharma M, Wakure A.Scar revision. Indian J Plast
Surg. 2013;46(2):408–18.
9. Shaw DT, Li CS.Multiple Y-V plasty. Ann Plast Surg.
1979;2(5):436–40.
10. Driscoll DN, Levy AN, Gama AR. Dermabrasion
and thin epidermal grafting for treatment of large
and small areas of postburn leukoderma: a case
series and review of the literature. J Burn Care Res.
2016;37(4):e387–93.
11. Negenborn VL, Groen JW, Smit JM, Niessen FB,
Mullender MG. The use of autologous fat grafting for treatment of scar tissue and scar-related
conditions: a systematic review. Plast Surg Nurs.
2016;36(3):131–43.
12. Gargano F, Schmidt S, Evangelista P, RobinsonBostom L, Harrington DT, Rossi K, etal. Burn scar
regeneration with the “SUFA” (subcision and fat
grafting) technique. A prospective clinical study.
JPRAS Open. 2018;17:5–8.
13. Kim WS, Park BS, Sung JH.The wound-healing and
antioxidant effects of adipose-derived stem cells.
Expert Opin Biol Ther. 2009;9(7):879–87.
14. Forcheron F, Agay D, Scherthan H, Riccobono D,
Herodin F, Meineke V, et al. Autologous adipocyte derived stem cells favour healing in a minipig
model of cutaneous radiation syndrome. PLoS One.
2012;7(2):e31694.
15. Kim WS, Park BS, Park SH, Kim HK, Sung
JH.Antiwrinkle effect of adipose-derived stem cell:
activation of dermal broblast by secretory factors. J
Dermatol Sci. 2009;53(2):96–102.
16. Si Z, Wang X, Sun C, Kang Y, Xu J, Wang X, etal.
Adipose-derived stem cells: sources, potency, and
implications for regenerative therapies. Biomed
Pharmacother. 2019;114:108765.
17. Jaspers MEH, Brouwer KM, van Trier AJM,
Middelkoop E, van Zuijlen PPM. Sustainable
effectiveness of single-treatment autologous fat
grafting in adherent scars. Wound Repair Regen.
2017;25(2):316–9.
18. Simonacci F, Bertozzi N, Grieco MP, Grignafni E,
Raposio E. Procedure, applications, and outcomes
of autologous fat grafting. Ann Med Surg (Lond).
2017;20:49–60.
19. Andreassi A, Bilenchi R, Biagioli M, D'Aniello
C.Classication and pathophysiology of skin grafts.
Clin Dermatol. 2005;23(4):332–7.
20. Wanner A, Adams C, Ratner D.Skin grafts. In: Rohrer
TE, Cook JL, Migden MR, editors. Flaps and grafts
in dermatologic surgery. Amsterdam: Elsevier; 2008.
p.107–16.
21. Herskovitz I, Hughes OB, Macquhae F, Rakosi A,
Kirsner R. Epidermal skin grafting. Int Wound J.
2016;13(Suppl 3):52–6.
Surgical Scar Therapy
https://t.me/med1917
193
22. Maderal AD, Kirsner RS. Clinical and economic
benets of autologous epidermal grafting. Cureus.
2016;8(11):e875.
23. Lebo PB, Grohmann M, Kamolz L. Delayed postburn scar reconstruction of the dorsum of the hand
with a collagen-elastin-based dermal substitute and
split-skin graft. Handchir Mikrochir Plast Chir.
2017;49(2):127–31.
24. Oh SJ, Kim Y.Combined AlloDerm(R) and thin skin
grafting for the treatment of postburn dyspigmented
scar contracture of the upper extremity. J Plast
Reconstr Aesthet Surg. 2011;64(2):229–33.
25. Yi JW, Kim JK. Prospective randomized comparison of scar appearances between cograft of acellular
dermal matrix with autologous split-thickness skin
and autologous split-thickness skin graft alone for
full-thickness skin defects of the extremities. Plast
Reconstr Surg. 2015;135(3):609e–16e.
26. Jung S, Oh SJ, Hoon KS.Hair follicle transplantation
on scar tissue. J Craniofac Surg. 2013;24(4):1239–41.
27. Kilic A, Kilic A, Emsen IM, Ozdengil E. Lip scars
camouaged using microhair transplantation on male
patients. Plast Reconstr Surg. 2000;106(6):1340–1.
28. Yoo H, Moh J, Park JU. Treatment of postsurgical
scalp scar deformity using follicular unit hair transplantation. Biomed Res Int. 2019;2019:3423657.
29. Lee LN. Hair transplant surgery and platelet rich
plasma. 1st ed. Cham: Springer International; 2020.
30. Akdag O, Evin N, Karamese M, Tosun
Z. Camouaging cleft lip scar using follicular unit extraction hair transplantation combined
with autologous fat grafting. Plast Reconstr Surg.
2018;141(1):148–51.
Further Reading
Hierner R, Putz R, Bishop AT, Shen Z, Wilhelm K.Flaps
in hand and upper limb reconstruction: surgical anatomy, operative techniques and differential therapy.
Amsterdam: Elsevier; 2016.
Strauch B, Yu H.Atlas of microvascular surgery: anatomy
and operative techniques. Stuttgart: Thieme; 2006.
Wanner A, Adams C, Ratner D.Chapter 9: Skin grafts. In:
Flaps and grafts in dermatologic surgery. Amsterdam:
Elsevier; 2008. p.107–16.
Zenn MR, Jones G. Reconstructive surgery: anatomy,
technique, and clinical application. Stuttgart: Thieme;
2012.
Oral Medication
https://t.me/med1917
Prevention andTherapy—Neurobiological
Management ofScars
VaritsaraMangkorntongsakul, AlanJ.Cooper,
andSaxonD.Smith
Core Messages
• Neuropathic pain and itch arise as a consequence of pathological processes within the
central nervous system (CNS) or through sensitisation of both CNS and the peripheral nervous system (PNS), resulting in chronic and
persistent symptoms.
• Tricyclic antidepressants (TCAs), duloxetine
and gabapentinoids are recommended as the
rst-line treatment for neuropathic pain based
on Grading of Recommendations Assessment,
Development, and Evaluation (GRADE)
recommendation.
V. Mangkorntongsakul (*)
Northern Clinical School, Sydney Medical School,
University of Sydney, Sydney, NSW, Australia
Gosford Hospital, Central Coast Local Health
District, Gosford, NSW, Australia
A. J. Cooper
Northern Clinical School, Sydney Medical School,
University of Sydney, Sydney, NSW, Australia
Department of Dermatology, Royal North Shore
Hospital, St Leonards, NSW, Australia
S. D. Smith
Northern Clinical School, Sydney Medical School,
University of Sydney, Sydney, NSW, Australia
Sydney Adventist Hospital Clinic School, ANU
Medical School, ANU College of Health and
Medicine, The Australian National University,
Canberra, ACT, Australia
The Dermatology and Skin Cancer Centre, St
Leonards, Sydney, NSW, Australia
• Antihistamines, including cetirizine, cimetidine and loratadine, are recommended as the
rst-line oral agents for both adult and paediatric patients based on GRADE classication.
• Ondansetron is recommended as a second-line
medication for the treatment of pruritus in
both adult and paediatric patients based on
GRADE classication.
Introduction
Pathological wound healing and scar formation
are major medical challenges causing signicant
psychological and physical distress. Not only do
they give rise to functional and aesthetic disadvantages, but scars can also result in various
degrees of sensation disturbances. The sensation
of itch and pain is closely related but also clearly
distinct. Dysfunction of the nervous system and
immune response will consequently lead to the
development of chronic symptoms of itchy and
painful scars, which have the capacity to become
increasingly complex and potentially more difcult to treat over time. Recent advances in pharmaceutical drug design and medical treatment
reveal numerous preventative and therapeutic
modalities to manage these chronic and disabling
symptoms. In this chapter, the authors reviewed
the current literature on oral pharmacological
approaches to symptoms of scar neuropathy,
mainly related to burn hypertrophic and keloid
scars, and prevention of acne scarring.
© The Author(s), under exclusive license to Springer Nature Switzerland AG 2024
S. P. Nischwitz et al. (eds.), Scars, https://doi.org/10.1007/978-3-031-24137-6_13
195
196
https://t.me/med1917
V. Mangkorntongsakul et al.
Pathophysiology ofPain andItch
inDermal Scar Tissues
Pain is dened as a distressing sensory and emotional experience associated with potential or
actual tissue damage [1]. Physiologically, this is
described as the activation of specialised primary
afferent neurons originating as free nerve endings
in the cutaneous tissues, namely myelinated
A-delta bres and subtypes of unmyelinated C
bre by a broad spectrum of painful neuromodulators. These include but are not limited to acetylcholine, bradykinin, adenosine triphosphate and
prostaglandin [2].
Following the depolarisation and activation of
action potentials, A-delta bres and C-bres
release the neurotransmitters (-glutamate) and
neuropeptides (glutamate, substance P and calcitonin gene-related peptide [CGRP]), respectively.
The impulse is then carried to the dorsal column
through the ascending pathway and forms a synapse with second-order neurons, which subsequently cross over to the contralateral side of the
ascending spinothalamic tract to reach the thalamus and pons and onto different parts of the
brain, evoking a withdrawal reex. Although they
play no role in acute pain activation, A-beta bres
are involved in the basis of chronic neuropathic
pain by modulating peripheral nociceptors under
the gate control theory of pain [3].
Pain can be categorised as acute or chronic as
determined by the duration of the symptoms or
nociceptive or non-nociceptive pain (neuropathic
or psychogenic) as determined by the underlying
pathophysiology [3].
Acute pain serves a protective purpose to prevent individuals from potentially hazardous situations. Chronic pain, however, has little protective
signicance and can cause distress if the pain
persists for three or more months despite normalisation after injury [4].
Nociceptive pain is a natural physiological
response towards a noxious stimulus through
activation or sensitisation of peripheral nociceptors. Once the stimuli are removed, the symptom
then subsides. Neuropathic pain, on the other
hand, arises as a consequence of pathological
processes within the central nervous system
(CNS) or through sensitisation of the peripheral
nervous system (PNS), resulting in chronic and
persistent pain—a frequently observed symptom
of scar tissues [2].
Itch (pruritus) is dened as an unpleasant
cutaneous sensation that provokes the desire to
scratch [5]. Itch can be a symptom of distinct skin
conditions or of occult underlying systemic diseases [6]. Itch can be classied into acute and
chronic with acute itch lasting less than 6weeks
and chronic itch lasting longer than 6 weeks.
However, in burn survivors, acute itch was proposed to last less than 3–6 months and chronic
itch can last up to 6months postburn injury [2, 7].
Itch can be further categorised into four subtypes
according to their underlying pathophysiology:
pruritoceptive, neuropathic, neurogenic and psychogenic [2, 6, 7].
Similar to pain, the mechanisms of itch can
originate from the CNS or peripheral nervous
system (PNS) [6]. The precise mechanism of pruritic scars is not well understood, but it has been
suggested to display a mixture of pruritogenic
and neuropathic features such as ongoing paresthesia [8]. Postburn pruritus has been shown to be
intractable to traditional treatment of antihistamine but is instead noted to be responsive to neuroleptic agents [9].
Following an injury, pruritoceptive itch arises
from pruritogenic neuromediators released from
cutaneous inammation and C-bres which are
mediated by various endogenous pruritogens.
These neuromediators work by directly stimulating nerve endings, activating the release of cytokines responsible for pruritic sensation or
sensitising the specialised C-bres [2, 6]. These
unmyelinated C-bres are anatomically identical
to those associated with the mediation of pain but
are functionally distinct [6].
C-bres are broadly categorised into two
groups based on mechanosensitivity: mechanically sensitive polymodal nociceptors (C
mechano- heat (CMH) nociceptor) and mechanically insensitive C-bres (C-MIAs) [10]. The
CMH nociceptor is the most common type of
C-bre which is associated with non-
Oral Medication
https://t.me/med1917
197
histaminergic mechanisms as this bre is either
insensitive to histamine or comparatively weak in
response to it. The bre also plays a role in a
mechanism of poor localisation and dull pain
sensation [6, 11]. C-MIAs, consisting of 5% of
all afferent C-bres, are thought to mediate
histamine- induced itch pathway. This is because
they vigorously respond to histamine and other
pruritogenic neuromediators but are unresponsive to mechanical stimuli [11]. They convey pruritic impulses to the dorsal horn of the spinal cord
and form a synapse with secondary neurons that
cross to the contralateral spinothalamic tract.
C-MIAs then ascend to the ventromedial and dorsomedial nuclei, and on to the somatosensory
cortex, producing the desire to scratch [6, 9, 11].
After an acute phase of wound healing, histamine is known to be less important to the pruritic mechanism. At the chronic stage,
neuropathic itch is proposed to be the main
underlying pathophysiology which is characterised by antihistamine-resistant wound with neural sensitisation [9].
While the differences in pain and itch are
apparent in acute settings, they share many similar mechanisms in chronic wounds involving
peripheral sensitisation as well as central sensitisation [13]. There are two mechanisms that have
been postulated to cause peripheral sensitisation
in chronic sensory phenomena in burn survivors:
the injured afferent hypothesis and the intact
nociceptor hypothesis.
The concept of injured afferent hypothesis
posits that neuropathic pain and itch may arise
from a neuroma, which is an injured primary
peripheral afferent nerve bre, resulting in disorganised growth of unmyelinated C bres from
injured axons. This leads to spontaneous excitability secondary to enhanced sensitivity to
mechanical, thermal and chemical stimuli [9, 14].
In the intact nociceptor hypothesis, it has been
suggested that uninjured nociceptors that innervate the area affected by the transacted nerve
bres become sensitised and develop spontaneous activity [2, 14].
In established central sensitisation, there is a
persistent autonomous activity in the CNS
related to aberrant somatosensory processing
which shifts maintenance into a chronic phase.
Several mechanisms have been hypothesised as
the basis of central sensitisation in neuropathic
phenomena, namely increased activity of dorsal
horn projection neurons, deafferentation theory,
loss of CNS inhibitory neurons, loss of descending inhibition and synaptic reorganisation
(Fig.1) [9].
The repetitive stimulation of the peripheral
nociceptor amplies nociceptive information,
which then causes an increase in activity of dor-
sal horn projection neurons of the spinal cord.
The afferent terminal then releases excitatory
neurotransmitter glutamate and substance P [1,
9]. A-beta bres are responsible for modulation
of nociceptor impulses and indirect interruption
of sensory transmission by inhibiting the effect of
nociceptive afferents. Following tissue injury,
loss of myelinated A-beta bres (deafferentation theory) input allows excess disinhibited
noxious stimuli to reach the CNS. Inhibitory
effects in the CNS are modulated by
γ-aminobutyric acid (GABA) interneurons in the
dorsal horn and descending pathway, which when
stimulated lead to inhibitory effects of nociceptors in laminae of the spinal cord [2, 9]. Thus,
loss of CNS inhibitory neurons and descending inhibition are linked to chronic sensory dis-
turbances through decreasing inhibition of
nociceptive pathway and increasing excitability
and sensitivity of the CNS. Furthermore, an
injury to the skin can lead to synaptic reorgan-
isation where neuronal loss or loss of synaptic
connection as deafferentation causes alterations
to the functional topography in the primary
somatosensory cortex. Thus, injured afferent
neurons mediate reorganisation that creates a distorted mapping of the skin [9, 15].
In neuropathic pain, prolonged repetitive activation of nociceptors not only leads to pain at the
site of the wound but also sensitises second-order
neurons in the dorsal horn. This combination
enhances the perception of cutaneous somatosensation due to a decrease in the threshold of painevoking stimuli. This is a natural phenomenon
known as primary hyperalgesia, which is largely
198
(deafferentation theory)input
Injured afferent/ intact
noci
https://t.me/med1917
V. Mangkorntongsakul et al.
Synaptic reorganisation of
somatosensory cortex
Loss of descending
pathway inhibitory
ceptor activity
Fig. 1 Schematic diagram of mechanisms underlying peripheral and central nervous system neuropathies. Adapted
from [2, 12]
related to the peripheral component of the nervous system.
Secondary hyperalgesia or allodynia, on the
other hand, is due to central sensitisation. The sensation is characterised by touch or brush- evoked
pain induced by typically innocuous mechanical
stimuli in the uninjured regions of an injury. This
occurs as a result of anatomical reorganisation in
which the primary afferent A-bres that normally
carry non-noxious stimuli gain access to activate the
pain pathway in dorsal horn neurons [1, 11]. These
pain sensitisation phenomena are analogous to the
itch dysesthesias, such as allokenesis and hyperkinesis, where itch is evoked by non-pruritic stimuli
and itch perception is intensied in response to itchinduced stimuli, respectively [11, 16].
Loss of myelinated A-beta fibres
Increase in activity
of dorsal horn
projection neurons
Loss of CNS inhibitory
neurons
Pharmacological Therapy forScar
Tissue Pain
Neuropathic pain arises from scar tissues and is
caused by injury to the afferent nerve resulting in
dysfunction of the somatosensory system [17].
To provide optimal therapeutic approach to painful scars, the management often involved a combination modality including both pharmacological
and non-pharmacological therapies. The current
evidence for oral pharmacotherapy of neuropathic painful scars, which is mainly related to
burn hypertrophic and keloid scars, supports the
use of tricyclic antidepressants (TCAs),
serotonin- norepinephrine reuptake inhibitors
(SNRIs), gabapentin and pregabalin. There is no
Oral Medication
https://t.me/med1917
199
consensus on the best therapeutic approach to
neuropathic pain due to scar tissues; thus there is
a need for a more comprehensive study, specically regarding neuropathic pain in scar tissues.
Antidepressants
Antidepressants are commonly prescribed for the
management of chronic neuropathic pain.
However, there have been limited studies investigating the efcacy of antidepressants in the management of scar pain. Chronic scar pain has a
component of neuropathic pain; thus, it can be
hypothesised that effective agents for neuropathic
pain may provide analgesic properties to attenuate pain in scar tissues. The coexistence of pain
and depression may be due to altered neuroplasticity and neurobiological mechanisms in the
CNS regions, which may be responsible for both
mood and peripheral pain [18]. Therefore, antidepressants can be a useful option in the treatment of neuropathic pain in individuals with
coexisting mood disorders.
Although the underlying mechanisms of antidepressant properties in neuropathic pain have
not been clearly delineated, the dosage of these
drugs for analgesia is lower than that for treating
depression, suggesting plausible different mechanisms of action. Increasing evidence has shown
that noradrenaline plays a vital role in the reduction of neuropathic pain. Inhibition of noradrenaline reuptake in the spinal cord has been shown
to have a direct analgesic effect on neuropathic
pain through α2-adrenergic receptors. It has
been observed that increasing the level of noradrenaline around the locus coeruleus improves
the impaired activity of the descending noradrenergic inhibitory system. Moreover, studies
have found that serotonin and dopamine may
facilitate the anti-neuropathic effects of noradrenaline [19].
Tricyclic antidepressants (TCAs) and
serotonin- norepinephrine reuptake inhibitor
(SNRIs), such as duloxetine, were recommended
as the rst-line treatment for neuropathic pain
based on strong Grading of Recommendations
Assessment, Development, and Evaluation
(GRADE) recommendations for use [20].
Tricyclic Antidepressants
Due to their lack of selectivity, TCAs have shown
to have superior therapeutic effects in the treatment of neuropathic pain compared to that of
SNRIs. However, the clinical use of TCAs is limited, in particular in elderly subjects, due to signicant side effects including potent anticholinergic
effects, sedation, postural hypotension and heart
block as well as fatal cardiac arrhythmia [21, 22].
Amitriptyline is believed to provide analgesic
control through inhibition of voltage-gated sodium
channels and serotonin-norepinephrine reuptake.
It may also have a direct effect on central sensitisation by blocking NMDA receptors in the spinal
cord which induces hyperalgesia [22, 23].
In 2017, an animal study conducted by Hiroki
etal. demonstrated that despite the suppression of
inhibitory descending noradrenergic system, amitriptyline still provides signicant antihyperalgesic properties through mediating
neurons inlocus coeruleus and enhances noradrenergic bre density. These ndings suggest that
amitriptyline may enhance the analgesic effect of
other neuropathic medications which requires an
intact descending noradrenergic inhibition pathway. Thus, this property makes amitriptyline a
potential effective analgesic option for combination therapy with SNRI and gabapentinoids [24].
These ndings may explain Gilron et al.
(2009)’s observation in their double-blind, randomised controlled, crossover trial with 56 subjects comparing the efcacy of nortriptyline and
gabapentin as monotherapy versus combination
therapy for neuropathic pain. A combination
therapy was found to be more efcacious than
either drug as monotherapy [25].
Nortriptyline, a secondary amine TCAs, has
shown equivalent benets to amitriptyline but was
found to be better tolerated with fewer toxicity proles [26, 27]. However, the available evidence to
support the claim that nortriptyline has less associated adverse effects remains inconsistent [27].
Serotonin-Norepinephrine Reuptake
Inhibitor
Duloxetine, a serotonin-norepinephrine reuptake
inhibitor (SNRI), also has been recommended as
a rst-line treatment based on GRADE recommendations due to consistent reports of its effec-
200
https://t.me/med1917
V. Mangkorntongsakul et al.
tive use in several neuropathic conditions namely
diabetic neuropathy, chronic lower back pain and
chemotherapy-induced peripheral neuropathy
[20, 28].
Minami etal. (2017) observed that duloxetine
may elicit analgesic effects mainly through the
activity in the monoamine system in the spinal
cord [29]. In their animal study, Ito etal. (2018)
also noted that duloxetine provided analgesic
effects against neuropathic pain by inhibiting the
accumulating effect of noradrenaline in the spinal
cord [30].
In 2019, Naja etal. conducted an open-label
randomised controlled trial that investigated the
analgesic effects of duloxetine dosed at 60mg/
day as a combination therapy to usual analgesic
regimens of morphine ± acetaminophen ± gabapentin in 46 burn survivors. Duloxetine was
found to enhance analgesic effects of other analgesic medications [21].
Selective Serotonin Reuptake
Inhibitors
The GRADE recommendations for SSRIs as the
treatment of neuropathic pain are inconclusive
due to contradictory ndings [20]. Lacking norepinephrine activity, SSRIs exert low analgesic
property in the inhibition of neuropathic pain.
However, there have been suggestions that SSRIs
may have auxiliary actions when given with noradrenaline reuptake inhibitors [31]. Due to their
receptor selectivity, SSRIs elicit less side effects
compared to other antidepressants. It can still be a
drug of choice for neuropathic pain patients with
mood disorder due to their better tolerability and
favourable side effect prole [32].
Neuroleptics
Pregabalin and gabapentin are classied as gabapentinoids due to their structural resemblance to
the inhibitory neurotransmitter gamma-aminobutyric acid (GABA); however, neither agent has
activity in GABAergic neuronal systems [33,
34]. Gabapentinoids are calcium channel antago-
nists that are characterised by high-afnity binding, selectively to alpha-2delta subunit
voltage-gated calcium channels. Through suppressing excitatory neurotransmitters, pregabalin
and gabapentin produce antiepileptic, analgesic
and anxiolytic properties [34–36]. They have
been recommended as a rst-line treatment for
various neuropathic pain syndrome such as diabetic neuropathy, post-herpetic neuralgia and
burn injury [33, 37, 38].
Gabapentin
Gabapentin specically affects the nociceptive
process involving in central sensitisation by suppressing glutamate and substance P transmission
as well as modulating GABA receptors [39]. The
evidence of the efcacy of gabapentin in the
management of acute burn pain and opioid consumption remains conicting. Several studies
reported the potential benet of gabapentin as an
adjunct to opioid analgesic therapy in the treatment of acute burn pain.
A double-blind randomised controlled trial
performed by Rimaz etal. (2012), assessing 50
burn patients with a single oral dose of gabapentin (1200 mg) or placebo 2 h prior to surgery,
demonstrated a statistically signicant overall
reduction in morphine requirement
(52.45 ± 10.4 mg in the placebo group to
33.8±18mg in the gabapentin group [p<0.05])
and pain scores (p <0.05) in gabapentin group
after surgical debridement in burn survivors [40].
The report was further supported by a retrospective observational study performed in
Belgium that investigated the opioid-sparing and
analgesic effects of gabapentin (2400mg in three
divided doses) in 10 severely burned patients
(mean total body surface area [TBSA] 25%) from
days 3 to 24. The study found an improvement in
mean daily pain scores and a reduction in opioid
requirements in patients receiving gabapentin
both during treatment (21days) and 21days posttreatment [39].
Notably, the analgesic effect of gabapentin
was exceeding the pharmacologic duration,
which was likely due to its ability to prevent central hyperalgesia [39, 41]. Consistent observation
of an improvement of acute burn pain in patients
receiving gabapentin was also made by another
case series study [42].
Oral Medication
https://t.me/med1917
201
However, Gustorff et al. (2004) conducted a
double-blinded placebo-controlled, crossover
study in 16 participants, evaluating the effects of
remifentanil and gabapentin on hyperalgesia in
an experimental supercial burn model and
observed neither anti-hyperalgesic nor opioidenhancing properties in gabapentin [43].
In 2014, a more recent randomised controlled
study assessed the efcacy of gabapentin in 50
burn survivors with TBSA of 5% and found that
gabapentin was ineffective as an analgesic
adjunct as its use did not reduce pain scores (rest
and procedural) or lessen opioid consumptions in
the acute burn period [44].
Pregabalin
Pregabalin is a newer analogue of gabapentin
with comparatively better pharmacokinetic proles including linear and dose-independent
absorption and a narrow therapeutic dosing range
[34, 45].
In 2010, Wong etal. conducted a retrospective
study of 13 outpatients with TBSA of 5% or more
receiving pregabalin in variable doses (maximum
600mg). In this series, a reduction of pain scores
up to 69% was noted in their treated participants
[46].
An Australian double-blind, randomised
placebo- controlled trial evaluated the efcacy
and tolerability of pregabalin in 90 inpatients
with moderate to severe burn injury and found
positive outcomes of pregabalin in the treatment
of postburn pain. Pregabalin was observed to be
well tolerated and effective with the starting dose
at 75mg twice daily and progressively increased
to 300mg twice per day in severe burn individuals who have features of acute neuropathic pain.
Interestingly, it was noted that an overall improvement of procedural pain was increased. The effect
was shown to be greatest during 3weeks of treatment with a reduction in pain score up to 40% in
the pooled data [47].
A retrospective review of pharmacy records
and charts noted pregabalin and gabapentin being
dispensed in variable doses starting at 50 mg
thrice daily for the management of neuropathic
pain and itch. The study included a total of 136
burn patients aged 10months to 20years old. Of
these 136 patients, 112 received only gabapentin,
none received only pregabalin while 24 received
both agents. Of the patients who only received
gabapentin, adequate response reported for pruritus and pain was 91.4% and 100%, respectively
while only 43.3% was reported for both symptoms. Of patients who received both gabapentin
and pregabalin, 88.2% noted adequate relief for
both symptoms [48].
In 2019, Jones et al. performed a prospective,
randomised, double-blinded, placebo-controlled
trail with 51 participants, comparing the efcacy
of 300mg pregabalin versus 600mg pregabalin
versus a placebo on acute postburn pain. In both
noncritical partial and full-thickness burn injuries, pregabalin was observed to be well tolerated
and dosing 600 mg of pregabalin per day provided superior pain control compared to 300mg
pregabalin per day (p<0.260). An overall opioid
consumption and pain values were lessened
across time, suggesting dosage amount of pregabalin may play a role in adequate pain management in burn care [47].
Clinical Tip
• Psychiatric patients who experience
neuropathic pain may benet from
antidepressants.
• Combination therapy of TCA and pregabalin/gabapentin can be used in
patients who are unresponsive to monotherapy or have intolerance to higher
doses of either drug.
• Combination of SNRIs and pregabalin/
gabapentin/morphine has been shown to
reduce intensity of neuropathic pain and
fewer side effects compared to monotherapy [49].
• Apart from combination therapy with
antidepressants, pregabalin/gabapentin
coupled with opioid has also shown to
be more effective in neuropathic pain.
202
https://t.me/med1917
Caution!
• Tricyclic antidepressants (TCAs) such
as amitriptyline and nortriptyline should
be used cautiously in elderly and cardiac
patients due to associated side effects.
• Treatment of gabapentinoids should be
taken with caution in particular in
elderly patients given its adverse effects
of dizziness and somnolence [45].
• TCAs have superior analgesic property
but carry more side effects compared to
those of SNRIs.
• Following the commencement of antidepressant, patients should be monitored
for emergence of suicidal ideation.
Pharmacological Therapy forScar
Tissue Itch
V. Mangkorntongsakul et al.
restricts daytime use of sedating antihistamines,
but they may have a role in nocturnal pruritus.
Second-generation H1-antihistamines have
become a preferable option given they are highly
selective for the H1-receptor with no anticholinergic effects. Thus, they are more efcacious
with a longer duration of action and favourable
safety proles [52, 53].
In adult postburn pruritus, the response rate of
antihistamines was varied, which could be attributable to the complexity of itch and multifactorial
pathophysiology that contribute to it in burn individuals. In participants who were treated with
antihistamines, 20% had their symptoms completely relieved, while 60% had partial relief and
20% had no relief of symptoms [15, 54]. A tolerance may develop in prolonged use of antihistamine therapy, although an increased dose and
temporary discontinuation of drug have shown to
effectively restore a response [8, 54].
Goutos et al. (2010) demonstrated that early
treatment with combination therapy consisting of
peripherally and centrally acting agents is often
required to achieve satisfactory relief in most
pruritic scar symptoms [50]. Oral therapy which
has been shown to improve the symptoms of pruritic scars to date includes antihistamine, naltrexone, antidepressants, neuroleptic agents and
ondansetron.
Antihistamine
Antihistamines are recommended as rst-line
pharmacological management of scar pruritus
[51]. H1-antihistamines are inverse agonists of
histamine H1-receptors, leading to the inactive
state of the H1-receptor. Antihistamines demonstrate anti-inammatory and anti-brotic properties on scars, reducing scar formation and
improving symptoms of pruritus [51].
Adverse drug reactions, commonly CNS
related, are mostly associated with rstgeneration H1-antihistamines due to their ability
to readily cross blood-brain barriers and interfere
with histaminergic transmission. Hence, this
Opioid Receptor Agonists or
Antagonists
Naltrexone, a μ-opioid antagonist, has been used
in the treatment of pruritus associated with different conditions including cholestasis, end- stage
renal disease and atopic dermatitis [55]. However,
the evidence regarding antipruritic effects on
postburn scars is yet to be established.
LaSalle et al. (2007) and Jung et at. (2009)
found a positive outcome of naltrexone in the
management of refractory pruritus with a high
percentage of patient satisfaction and associated
improvement in their quality of life [56, 57]. The
mechanism of action of naltrexone is unclear. It
was observed that μ-opioid receptor agonists
induced the symptoms of pruritus which can be
revered by μ-opioid receptor antagonists, suggesting an imbalance of endogenous opioidergic
system, in particular central origin, may link to
the underlying pathophysiology of pruritus [56].
A randomised crossover trial by Peer et al.
(1996) demonstrated a signicant reduction of
plasma histamine in uremic patients who were
treated with naltrexone. In their experiment, naltrexone was observed to inhibit histamine release
Соседние файлы в папке @xirurgi_2025